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In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area. [ABSTRACT FROM AUTHOR]

Ongoing research is gradually broadening the idea of cancer treatment, with attention being focused on nanoparticles to improve the stability, therapeutic efficacy, targeting, and other important metrics of conventional drugs and traditional drug delivery methods. Studies have demonstrated that drug delivery carriers based on biomaterials (e.g., protein nanoparticles and lipids) and inorganic materials (e.g., metal nanoparticles) have potential anticancer effects. Among these carriers, self-assembled proteins and peptides, which are highly biocompatible and easy to standardize and produce, are strong candidates for the preparation of anticancer drugs. Breast cancer (BC) and cervical cancer (CC) are two of the most common and deadly cancers in women. These cancers not only threaten lives globally but also put a heavy burden on the healthcare system. Despite advances in medical care, the incidence of these two cancers, particularly CC, which is almost entirely preventable, continues to rise, and the mortality rate remains steady. Therefore, there is still a need for in-depth research on these two cancers to develop more targeted, efficacious, and safe therapies. This paper reviews the types of self-assembling proteins and peptides (e.g., ferritin, albumin, and virus-like particles) and natural products (e.g., soy and paclitaxel) commonly used in the treatment of BC and CC and describes the types of drugs that can be delivered using self-assembling proteins and peptides as carriers (e.g., siRNAs, DNA, plasmids, and mRNAs). The mechanisms (including self-assembly) by which the natural products act on CC and BC are discussed. The mechanism of action of natural products on CC and BC and the mechanism of action of self-assembled proteins and peptides have many similarities (e.g., NF-KB and Wnt). Thus, natural products using self-assembled proteins and peptides as carriers show potential for the treatment of BC and CC. [ABSTRACT FROM AUTHOR]

The thermostable protease TTHA0724 derived from Thermus thermophilus HB8 is an ideal industrial washing enzyme due to its thermophilic characteristics; although it can be expressed in Escherichia coli via pET-22b, high yields are difficult to achieve, leading to frequent autolysis of the host. This paper details the development of a signal peptide library in the expression system of B. subtilis and the optimization of signal peptides for enhanced extracellular expression of TTHA0724. When B. subtilis was used as the host and the optimized signal peptide was used, the expression level of TTHA0724 was 16.7 times higher compared with E. coli. B. subtilis as an expression host does not change the characteristics of TTHA0724. The potential application fields of TTHA0724 are studied. TTHA0724 can be used as a detergent additive at 60 °C, which can sterilize and eliminate mites while thoroughly cleaning protein stains. Soybean meal enzymatic hydrolysis with TTHA0724 at a high temperature produced a higher content of antioxidant peptides. These results indicate that TTHA0724 has great potential for industrial applications. [ABSTRACT FROM AUTHOR]

Charge variants, as an important quality attribute of mAbs, must be comprehensively characterized and monitored during development. However, due to their complex structure, the characterization of charge variants is challenging, labor-intensive, and time-consuming when using traditional approaches. This work combines on-line and off-line 2D-LC-MS to comprehensively characterize mAb charge variants and quickly offer precise instructions for process development. Six charge variant peaks of mAb 1 were identified using the developed platform. Off-line 2D-LC-MS analysis at the peptide level showed that the acidic peak P1 and the basic peaks P4 and P5 were caused by the deamidation of asparagine, the oxidation of methionine, and incomplete C-terminal K loss, respectively. On-line 2D-LC-MS at the intact protein level was used to identify the root causes, and it was found that the acidic peak P2 and the basic peak P6 were due to the glutathionylation of cysteine and succinimidation of aspartic acid, respectively, which were not found in off-line 2D-LC-MS because of the loss occurring during pre-treatment. These results suggest that process development could focus on cell culture for adjustment of glutathionylation. In this paper, we propose the concept of precision process development based on on-line 2D-LC-MS, which could quickly offer useful data with only 0.6 mg mAb within 6 h for precise instructions for process development. Overall, the combination of on-line and off-line 2D-LC-MS can characterize mAb charge variants more comprehensively, precisely, and quickly than other approaches. This is a very effective platform with routine operations that provides precise instructions for process development within hours, and will help to accelerate the development of innovative therapeutics. [ABSTRACT FROM AUTHOR]

Cancer is one of the major diseases that seriously threaten human life. Traditional anticancer therapies have achieved remarkable efficacy but have also some unavoidable side effects. Therefore, more and more research focuses on highly effective and less-toxic anticancer substances of natural origin. Amphibian skin is rich in active substances such as biogenic amines, alkaloids, alcohols, esters, peptides, and proteins, which play a role in various aspects such as anti-inflammatory, immunomodulatory, and anticancer functions, and are one of the critical sources of anticancer substances. Currently, a range of natural anticancer substances are known from various amphibians. This paper aims to review the physicochemical properties, anticancer mechanisms, and potential applications of these peptides and proteins to advance the identification and therapeutic use of natural anticancer agents. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a pregnancy-specific disorder affecting 4–10% of all expectant women. It greatly increases the risk of maternal and foetal death. Although the main symptoms generally appear after week 20 of gestation, scientific studies indicate that the mechanism underpinning PE is initiated at the beginning of gestation. It is known that the pathomechanism of preeclampsia is strongly related to inflammation and oxidative stress, which influence placentation and provoke endothelial dysfunction in the mother. However, as of yet, no "key players" regulating all these processes have been discovered. This might be why current therapeutic strategies intended for prevention or treatment are not fully effective, and the only effective method to stop the disease is the premature induction of delivery, mostly by caesarean section. Therefore, there is a need for further research into new pharmacological strategies for the treatment and prevention of preeclampsia. This review presents new preventive methods and therapies for PE not yet recommended by obstetrical and gynaecological societies. As many of these therapies are in preclinical studies or under evaluation in clinical trials, this paper reports the molecular targets of the tested agents or methods. [ABSTRACT FROM AUTHOR]

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate. [ABSTRACT FROM AUTHOR]

Various lung diseases endanger people's health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future. [ABSTRACT FROM AUTHOR]

Temporins are short peptides secreted by frogs from all over the world. They exert antimicrobial activity, mainly against Gram-positive bacteria, including resistant pathogens; recent studies highlight other possible applications of these peptides as anticancer or antiviral agents. This review is meant to describe the main features of temporins produced by different ranid genera. Due to the abundance of published papers, we focus on the most widely investigated peptides. We report studies on their mechanism of action and three-dimensional structure in model systems mimicking bacterial membranes or in the presence of cells. The design and the antimicrobial activity of peptide analogues is also described, with the aim of highlighting elements that are crucial to improve the bioactivity of peptides while reducing their toxicity. Finally, a short section is dedicated to the studies aimed at applying these peptides as drugs, to produce new antimicrobial materials or in other technological uses. [ABSTRACT FROM AUTHOR]

In this paper we study two lysine-based peptide dendrimers with Lys-His-Arg and Lys-Arg-His repeating units and terminal lysine groups. Combination of His and Arg properties in a dendrimer could be important for biomedical applications, especially for prevention of dendrimer aggregation and for penetration of dendrimers through various cell membranes. We describe the synthesis of these dendrimers and the confirmation of their structure using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. NMR spectroscopy and relaxation are used to study the structural and dynamic properties of these macromolecules and to compare them with properties of previously studied dendrimers with Lys-2Arg and Lys-2His repeating units. Our results demonstrate that both Lys-His-Arg and Lys-Arg-His dendrimers have pH sensitive conformation and dynamics. However, properties of Lys-His-Arg at normal pH are more similar to those of the more hydrophobic Lys-2His dendrimer, which has tendency towards aggregation, while the Lys-Arg-His dendrimer is more hydrophilic. Thus, the conformation with the same amino acid composition of Lys-His-Arg is more pH sensitive than Lys-Arg-His, while the presence of Arg groups undoubtedly increases its hydrophilicity compared to Lys-2His. Hence, the Lys-His-Arg dendrimer could be a more suitable (in comparison with Lys-2His and Lys-Arg-His) candidate as a pH sensitive nanocontainer for drug delivery. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, characterised by the accumulation of senile plaques and tau tangles, neurodegeneration, and neuroinflammation in the brain. The development of AD is a pathological cascade starting according to the amyloid hypothesis with the accumulation and aggregation of the β-amyloid peptide (Aβ), which induces hyperphosphorylation of tau and promotes the pro-inflammatory activation of microglia leading to synaptic loss and, ultimately, neuronal death. Modelling AD-related processes is important for both studying the molecular basis of the disease and the development of novel therapeutics. The replication of these processes is often achieved with the use of a purified Aβ peptide. However, Aβ preparations obtained from different sources can have strikingly different properties. This review aims to compare the structure and biological effects of Aβ oligomers and aggregates of a higher order: synthetic, recombinant, purified from cell culture, or extracted from brain tissue. The authors summarise the applicability of Aβ preparations for modelling Aβ aggregation, neurotoxicity, cytoskeleton damage, receptor toxicity in vitro and cerebral amyloidosis, synaptic plasticity disruption, and cognitive impairment in vivo and ex vivo. Further, the paper discusses the causes of the reported differences in the effect of Aβ obtained from the sources mentioned above. This review points to the importance of the source of Aβ for AD modelling and could help researchers to choose the optimal way to model the Aβ-induced abnormalities. [ABSTRACT FROM AUTHOR]

Amyloid-β peptide (Aβ) aggregates are known to be correlated with pathological neurodegenerative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro Aβ42 fibril formation in the presence of cortisol at different relative concentrations. The thioflavin T fluorescence assay allowed us to monitor the fibril formation kinetics, while a morphological characterization of the aggregates was obtained by atomic force microscopy. Moreover, infrared absorption spectroscopy was exploited to investigate the secondary structure changes along the fibril formation path. Molecular dynamics calculations allowed us to understand the intermolecular interactions with cortisol. The combined results demonstrated the influence of cortisol on the fibril formation process: indeed, at cortisol-Aβ42 concentration ratio (ρ) close to 0.1 a faster organization of Aβ42 fragments into fibrils is promoted, while for ρ = 1 the formation of fibrils is completely inhibited. [ABSTRACT FROM AUTHOR]

Amyloid fibrils have been known for many years. Unfortunately, their fame stems from negative aspects related to amyloid diseases. Nevertheless, due to their properties, they can be used as interesting nanomaterials. Apart from their remarkable stability, amyloid fibrils may be regarded as a kind of a storage medium and as a source of active peptides. In many cases, their structure may guarantee a controlled and slow release of peptides in their active form; therefore, they can be used as a potential nanomaterial in drug delivery systems. In addition, amyloid fibrils display controllable stiffness, flexibility, and satisfactory mechanical strength. In addition, they can be modified and functionalized very easily. Understanding the structure and genesis of amyloid assemblies derived from a broad range of amyloidogenic proteins could help to better understand and use this unique material. One of the factors responsible for amyloid aggregation is the steric zipper. Here, we report the discovery of steric zipper-forming peptides in the sequence of the amyloidogenic protein, human cystatin C (HCC). The ability of short peptides derived from this fragment of HCC to form fibrillar structures with defined self-association characteristics and the factors influencing this aggregation are also presented in this paper. [ABSTRACT FROM AUTHOR]

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. [ABSTRACT FROM AUTHOR]

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated as a hypothalamic peptide based on its efficacy to increase adenylate cyclase (AC) activity. It has a widespread distribution throughout the body including the nervous system and peripheral organs, where PACAP exerts protective effects both in vivo and in vitro through its anti-apoptotic, anti-inflammatory, and antioxidant functions. The aim of the present paper was to review the currently available literature regarding the effects of PACAP on cell death in vitro in neural and non-neural cells. Among others, its effect on apoptosis can be detected in cerebellar granule cells against different toxic stimuli. Different neural cell types from the cerebral cortex are also prevented from cell death. PACAP also shows effects on cell death in cells belonging to the peripheral nervous system and protects both neural and non-neural cells of sensory organs. In addition, cell survival-promoting effect can be observed in different peripheral organ systems including cardiovascular, immune, respiratory, gastrointestinal, urinary, and reproductive systems. The studies summarized here indicate its noteworthy effect on cell death in different in vitro models, suggesting PACAP's potential therapeutic usage in several pathological conditions. [ABSTRACT FROM AUTHOR]

Oligonucleotide–peptide conjugates (OPCs) are a promising class of biologically active compounds with proven potential for improving nucleic acid therapeutics. OPCs are commonly recognized as an efficient instrument to enhance the cellular delivery of therapeutic nucleic acids. In addition to this application field, OPCs have an as yet unexplored potential for the post-SELEX optimization of DNA aptamers. In this paper, we report the preparation of designer thrombin aptamer OPCs with peptide side chains anchored to a particular thymidine residue of the aptamer. The current conjugation strategy utilizes unmodified short peptides and support-bound protected oligonucleotides with activated carboxyl functionality at the T3 thymine nucleobase. The respective modification of the oligonucleotide strand was implemented using N3-derivatized thymidine phosphoramidite. Aptamer OPCs retained the G-quadruplex architecture of the parent DNA structure and showed minor to moderate stabilization. In a series of five OPCs, conjugates bearing T3–Ser–Phe–Asn (SFN) or T3–Tyr–Trp–Asn (YWN) side chains exhibited considerably improved anticoagulant characteristics. Molecular dynamics studies of the aptamer OPC complexes with thrombin revealed the roles of the amino acid nature and sequence in the peptide subunit in modulating the anticoagulant activity. [ABSTRACT FROM AUTHOR]

The investigated compounds inhibited A SB 21-40 sb aggregation and modulated the peptide disaggregation via the formation of adducts where the metal center loses chloride ligands. Altogether, these new studies show once again the importance of metals in regulating the activity and function of peptides, and the importance of studying metal compounds endowed with unique biological properties. At a physiological pH, NGF peptides bind copper ion with a higher affinity than N-terminal peptides of A , and a lower affinity than that observed for peptides derived from human copper transporter 1 (hCtr1), the protein responsible for copper uptake in neurons. Three papers in the Special Issue report studies based on metals or metal compounds and peptide recognition processes. [Extracted from the article]

In the eighth manuscript, Santos and co-workers [[8]] reported a novel casein-derived antibacterial polypeptide produced through a cheese whey fermentation methodology and capable of inhibiting matrix metalloproteases MMP-2 and MMP-9. The seventh paper, authored by Abioye and co-workers [[7]], reported the identification of three tetrapeptides, TNGQ, MANT, and YMSV, which inhibited islet amyloid polypeptide fibrillation. This Special Issue of the I International Journal of Molecular Sciences i is focused on bioactive peptides in foods or hydrolyzates of food by-products, the methods for the extraction and purification of bioactive peptides, their structural and functional characterization, and the mechanisms of action that regulate their activity and support the reported health benefits. [Extracted from the article]

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent. [ABSTRACT FROM AUTHOR]

Lipopeptides produced by microorganisms are one of the five major classes of biosurfactants known and they have received much attention from scientific and industrial communities due to their powerful interfacial and biological activities as well as environmentally friendly characteristics. Microbially produced lipopeptides are a series of chemical structural analogues of different families and, among them, 26 families covering about 90 lipopeptide compounds have been reported in the last two decades. This paper reviews the chemical structural characteristics and molecular behaviors of surfactin, one of the representative lipopeptides of the 26 families. In particular, two novel surfactin molecules isolated from cell-free cultures of Bacillus subtilis HSO121 are presented. Surfactins exhibit strong self-assembly ability to form sphere-like micelles and larger aggregates at very low concentrations. The amphipathic and surface properties of surfactins are related to the existence of the minor polar and major hydrophobic domains in the three 3-D conformations. In addition, the application potential of surfactin in bioremediation of oil spills and oil contaminants, and microbial enhanced oil recovery are discussed. [ABSTRACT FROM AUTHOR]

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens. [ABSTRACT FROM AUTHOR]

In recent years, some exogenous bioactive peptides have been shown to have promising anti-aging effects. These exogenous peptides may have a mechanism similar to endogenous peptides, and some can even regulate the release of endogenous active peptides and play a synergistic role with endogenous active peptides. Most aging studies use rodents that are easy to maintain in the laboratory and have relatively homogenous genotypes. Moreover, many of the anti-aging studies using bioactive peptides in rodent models only focus on the activity of single endogenous or exogenous active peptides, while the regulatory effects of exogenous active peptides on endogenous active peptides remain largely under-investigated. Furthermore, the anti-aging activity studies only focus on the effects of these bioactive peptides in individual organs or systems. However, the pathological changes of one organ can usually lead to multi-organ complications. Some anti-aging bioactive peptides could be used for rescuing the multi-organ damage associated with aging. In this paper, we review recent reports on the anti-aging effects of bioactive peptides in rodents and summarize the mechanism of action for these peptides, as well as discuss the regulation of exogenous active peptides on endogenous active peptides. [ABSTRACT FROM AUTHOR]

Crkl is a protein involved in the onset of several cancer pathologies that exerts its function only through its protein–protein interaction domains, a SH2 domain and two SH3 domains. SH3 domains are small protein interaction modules that mediate the binding and recognition of proline-rich sequences. One of the main physiological interactors of Crkl is C3G (also known as RAPGEF1), an interaction with key implications in regulating cellular growth and differentiation, cell morphogenesis and adhesion processes. Thus, understanding the interaction between Crkl and C3G is fundamental to gaining information about the molecular determinants of the several cancer pathologies in which these proteins are involved. In this paper, through a combination of fast kinetics at different experimental conditions and site-directed mutagenesis, we characterize the binding reaction between the N-SH3 domain of Crkl and a peptide mimicking a specific portion of C3G. Our results show a clear effect of pH on the stability of the complex, due to the protonation of negatively charged residues in the binding pocket of N-SH3. Our results are discussed under the light of previous work on SH3 domains. [ABSTRACT FROM AUTHOR]

Botany-derived antimicrobial peptides (BAMPs), a class of small, cysteine-rich peptides produced in plants, are an important component of the plant immune system. Both in vivo and in vitro experiments have demonstrated their powerful antimicrobial activity. Besides in plants, BAMPs have cross-kingdom applications in human health, with toxic and/or inhibitory effects against a variety of tumor cells and viruses. With their diverse molecular structures, broad-spectrum antimicrobial activity, multiple mechanisms of action, and low cytotoxicity, BAMPs provide ideal backbones for drug design, and are potential candidates for plant protection and disease treatment. Lots of original research has elucidated the properties and antimicrobial mechanisms of BAMPs, and characterized their surface receptors and in vivo targets in pathogens. In this paper, we review and introduce five kinds of representative BAMPs belonging to the pathogenesis-related protein family, dissect their antifungal, antiviral, and anticancer mechanisms, and forecast their prospects in agriculture and global human health. Through the deeper understanding of BAMPs, we provide novel insights for their applications in broad-spectrum and durable plant disease prevention and control, and an outlook on the use of BAMPs in anticancer and antiviral drug design. [ABSTRACT FROM AUTHOR]

In this paper, we present findings from studying the interaction of copper(II) ions with the His2-cyclopentapeptide and the role of proline used for the purpose of potentiometric titration and UV-Vis, CD and EPR spectroscopic measurements. Experiments of two homodetic peptides differing by one amino acid residue were conducted for a ligand to metal ratio of 1:1 in the pH range 2.5–11.0. The presented studies reveal that peptides form only mononuclear complexes, and the CuH2L complex appears in the system first (for both L1 and L2). Study results show that the presence of Pro influences the structure of formed complexes and their stabilities and has a strong impact on the efficiency of copper(II) coordination. [ABSTRACT FROM AUTHOR]

Understanding the kinetics of peptide self-assembly is important because of the involvement of peptide amyloid fibrils in several neurodegenerative diseases. In this paper, we have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench. Due to the low concentrations involved, the experimental method of choice was isothermal titration calorimetry (ITC). We show that the dissolution is a strikingly slow and reaction-limited process, that can be timescale separated from other rapid processes associated with dilution in the ITC experiment. We argue that the rate-limiting step of dissolution involves the breaking up of inter-peptide β –sheet hydrogen bonds, replacing them with peptide–water hydrogen bonds. Complementary pH experiments revealed that the self-assembly involves partial deprotonation of the peptide molecules. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptors associate into dimers/oligomers whose function is not well understood. One approach to investigate this issue is to challenge oligomerization by peptides replicating transmembrane domains and to study their effect on receptor functionality. The disruptor peptides are typically delivered by means of cell-penetrating vectors such as the human immunodeficiency virus (HIV) transcription trans-activation protein Tat. In this paper we report a cyclic, Tat-like peptide that significantly improves its linear analogue in targeting interreceptor sequences in the transmembrane space. The same cyclic Tat-like vector fused to a transmembrane region not involved in receptor oligomerization was totally ineffective. Besides higher efficacy, the cyclic version has enhanced proteolytic stability, as shown by trypsin digestion experiments. [ABSTRACT FROM AUTHOR]

Burns are physically debilitating and potentially fatal injuries. Two marine biomaterials, carboxymethyl chitosan (CMC) and collagen peptides (COP), have emerged as promising burn dressings. In this paper, sponges of carboxymethyl chitosan grafted with collagen peptide (CMC–COP) were prepared by covalent coupling and freeze drying. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were then used to characterize the prepared sponges. To evaluate the wound healing activity of the CMC–COP sponges, in vitro tests including cell viability scratch wound healing and scald wound healing experiments were performed in rabbits. Appearance studies revealed the porous nature of sponges and FTIR spectroscopy demonstrated the successful incorporation of COP into CMC. The in vitro scratch assay showed that treatment with CMC–COP sponges (at 100 μg/mL) had significant effects on scratch closure. For burn wounds treated with CMC–COP, regeneration of the epidermis and collagen fiber deposition was observed on day 7, with complete healing of the epidermis and wound on days 14 and 21, respectively. Based on the pathological examination by hematoxylin and eosinstaining, the CMC–COP group demonstrated pronounced wound healing efficiencies. These results confirmed that the CMC–COP treatment enhanced cell migration and promoted skin regeneration, thereby highlighting the potential application of these sponges in burn care. [ABSTRACT FROM AUTHOR]

The growing integration of quality-by-design (QbD) concepts in biomanufacturing calls for a detailed and quantitative knowledge of the profile of impurities and their impact on the product safety and efficacy. Particularly valuable is the determination of the residual level of host cell proteins (HCPs) secreted, together with the product of interest, by the recombinant cells utilized for production. Though often referred to as a single impurity, HCPs comprise a variety of species with diverse abundance, size, function, and composition. The clearance of these impurities is a complex issue due to their cell line to cell line, product-to-product, and batch-to-batch variations. Improvements in HCP monitoring through proteomic-based methods have led to identification of a subset of "problematic" HCPs that are particularly challenging to remove, both at the product capture and product polishing steps, and compromise product stability and safety even at trace concentrations. This paper describes the development of synthetic peptide ligands capable of capturing a broad spectrum of Chinese hamster ovary (CHO) HCPs with a combination of peptide species that allow for advanced mixed-mode binding. Solid phase peptide libraries were screened for identification and characterization of peptides that capture CHO HCPs while showing minimal binding of human IgG, utilized here as a model product. Tetrameric and hexameric ligands featuring either multipolar or hydrophobic/positive amino acid compositions were found to be the most effective. Tetrameric multipolar ligands exhibited the highest targeted binding ratio (ratio of HCP clearance over IgG loss), more than double that of commercial mixed-mode and anion exchange resins utilized by industry for IgG polishing. All peptide resins tested showed preferential binding to HCPs compared to IgG, indicating potential uses in flow-through mode or weak-partitioning-mode chromatography. [ABSTRACT FROM AUTHOR]