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Cationic amphipathic structures are often utilized in natural membrane-active host-defense peptides. Negatively charged surface membranes of rapidly proliferating bacterial and cancer cells have been targeted by various synthetic peptides and peptidomimetics adopting the structural motif. Herein, we synthesized a set of conjugates composed of cationic amphipathic peptoids (i.e., oligo-N-substituted glycines) and a chlorin photosensitizer, named chlorin e6 (Ce6)-peptoid conjugates (CPCs). Among the nine CPCs, CPC 7, composed of Ce6, a PEG linker, and guanidine-rich helical amphipathic peptoids, exhibited a distinct photoresponsive inactivation of Gram-positive and Gram-negative bacteria. Subsequent studies showed that CPC 7 effectively killed various cancer cells after irradiation with red light (655 nm), suggesting the potential of CPC 7 as a dual antimicrobial and anticancer agent. Confocal laser scanning microscopy and flow cytometry data suggested that CPC 7 could induce apoptotic cell death. Our results show the potential of peptoid-based photosensitizer conjugates as a versatile platform for antimicrobial and anticancer photodynamic therapy agents and peptoid therapeutics. [ABSTRACT FROM AUTHOR]

Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry. However, the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge. Herein, we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle (pepsomes) with an average diameter of ∼180 nm. Both cryo-transmission electron microscopy (TEM) and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around ∼1.6 nm. The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet (UV) and visible lights, which was attributable to the photoisomerization virtue of azobenzene moiety. As a proof-of-concept, the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol. Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles. Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis. [ABSTRACT FROM AUTHOR]

Natural antifreeze proteins are known for their excellent control of ice formation and growth, while synthetic molecules seldom have the similar effects. Here we report a series of protein mimetic peptoids with different side chains exhibiting significant ice recrystallization inhibition activity, and their structure–property relationships are also studied. The presence of peptoid can clearly slow down ice growth and decrease ice crystal grain size, but shows no thermal hysteresis, which make peptoids great antifreeze agent candidates in cryopreservation. Peptoids with methyl, ethyl and amino groups on side chains can modulate ice crystal shape, while peptoids bearing hydroxyl and ethyl groups decrease ice growth rate the most. All peptoids can reduce ice crystal grain size and the one with hydroxyl groups give the smallest grain size. This study reveals peptoid structure effects on ice growth and points to the design rules for biomimetic antifreeze agents. [ABSTRACT FROM AUTHOR]

The development of low fouling membranes to minimize protein adsorption has relevance in various biomedical applications. Here, electrically neutral peptoids containing 2-methoxyethyl glycine (NMEG) side chains were attached to polysulfone hollow fiber membranes via polydopamine. The number of side chains and grafting density were varied to determine the effect on coating properties and the ability to prevent fouling. NMEG peptoid coatings have high hydrophilicity compared to unmodified polysulfone membranes. The extent of biofouling was evaluated using bovine serum albumin, as well as platelet adhesion. The results suggest that both the number of side chains and grafting density play a role in the surface properties that drive biofouling. Protein adsorption decreased with increasing peptoid grafting density and is lowest above a critical grafting density specific to peptoid chain length. Our findings show that the optimization of grafting density and hydration of the surface are important factors for achieving the desired antifouling performance. [ABSTRACT FROM AUTHOR]

Tuberculosis has become a cause of worldwide concern; emergence of resistance in various mycobacterial strains has led to an urgent demand for new therapeutic molecules. Antimicrobial peptides have emerged as potential candidates in antimicrobial drug development. We have tested a lead antibacterial peptide LP-23 and its cost-effective mimetic DP-23 for their antimicrobial effects in a non-pathogenic model of Mycobacterium. Their minimum inhibitory concentration (MIC) values against M. smegmatis were calculated by resazurin reduction assay. MIC of both peptidomimetics against M. smegmatis was found to be 6.25 μg/mL. In addition, hemolytic toxicity study of peptidomimetics suggested that the synthesized compounds were selective against bacteria. To better understand stability and mechanism of action of peptidomimetics, serum stability study and SEM analysis were carried out. Peptoid DP-23 was found to be more stable in serum then peptide LP-23, while SEM analysis indicated that these compounds target the cell membrane, impairing the membrane integrity of M. smegmatis. The activity and properties of LP-23 and DP-23 may make them new potential antibacterial agents against tuberculosis. [ABSTRACT FROM AUTHOR]

Peptoids are a class of peptidomimetics whose pharmacological activities are widely investigated owing to their remarkable biological stability. However, the utilities of peptoids as cosmetic functional ingredients have not been fully explored. Here, we investigated anti-aging effects of PAL-12, a new hexa-peptoid, on UVB-induced photoaging in human dermal fibroblasts (HDFs) and a 3D reconstituted human full skin model, Keraskin-FT™. PAL-12 suppressed matrix metalloproteinase-1 (MMP-1) expression induced by UVB irradiation along with the attenuation of MMP-1 secretion as determined by ELISA assay. Interestingly PAL-12 slightly enhanced the expression levels of collagen-1 and fibronectin-1 in HDFs or Keraskin-FT™. In addition, PAL-12 prevented the decrease of cell viability following UVB irradiation. However, PAL-12 failed to affect ROS generation, cell necrosis and apoptosis significantly. Instead, PAL-12 suppressed UVB-induced activation of epidermal growth factor receptors (EGFR), extracellular signal-regulated kinase (ERK) and c-Jun, which may resulted in the attenuation of AP-1-promoted MMP-1 expression. Collectively, these results suggest that PAL-12 might be a novel cosmetic ingredient effective against UVB-induced skin photoaging. [ABSTRACT FROM AUTHOR]

Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate effectively interact with autoreactive antibodies, which attests to their high therapeutic potential. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possibility of immobilizing peptoid on chitosan film in order to generate new active material. Chitosan films have been grafted for the first time with short-length peptoid oligomers displaying antioxidant activities. The antioxidant activity of the selected peptoids was initially investigated with the DPPH assay and hydroxyl radical procedure. The metal chelating capacity of peptoids was also evaluated prior to their covalent attachment to chitosan. The benefit of chitosan functionalization with respect to its intrinsic antioxidant properties was finally evaluated in the present study. Interestingly, an increase of up to 90 % of the antioxidant activity of chitosan was observed. [ABSTRACT FROM AUTHOR]

The ability to calculate molecular properties such as molecular weights, isoelectric points, and extinction coefficients is vital for scientists using and/or synthesizing peptides and peptoids for research. A suite of two web utilities: Peptide Calculator and Peptoid Calculator, available free at , are presented. Both tools allow the calculation of peptide/peptoid chemical formulae and molecular weight, ChemDraw structure file export and automatic assignment of mass spectral peaks to deletion sequences and metal/protecting group adducts. Peptide Calculator also provides a calculated isoelectric point, molar extinction coefficient, graphical peptide charge summary and β-strand contiguity profile (for aggregation-prone sequences), indicating potential regions of synthesis difficulty. In addition to the unique automatic spectral assignment features offered across both utilities, Peptoid Calculator represents a first-of-a-kind resource for researchers in the field of peptoid science. With a constantly expanding database of over 120 amino acids, non-natural peptide building blocks and peptoid building blocks, it is anticipated that Pep-Calc.com will act as a valuable asset to those working on the synthesis and/or application of peptides and peptoids in the biophysical and life sciences fields. [ABSTRACT FROM AUTHOR]

Diverse compound sources are being explored for de-pigmentation activities to develop novel therapeutic agents or functional cosmetic ingredients for hyper-pigmentation disorders. Peptoids are a class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, instead of α-carbon. Peptoids are more durable against proteolysis and are being actively investigated in drug discovery, but rarely studied as cosmetic ingredients. Here, we demonstrated that new hexa-peptoids, PAL-10 and PAL-12, can inhibit melanogenesis in B16F10 melanoma cells, a 3D pigmented human skin model (Neoderm-ME, Tegoscience Co) and zebrafish. Anti-melanogenic effects of PAL-10 or PAL-12 as compared with arbutin, a positive control in B16F10 cells, Neoderm-ME and zebrafish were statistically significant and concentration-dependent anti-melanogenic effects were manifested as determined by image, histology, and melanin contents. Anti-melanogenic effects of PAL-10 appeared to be from enzymatic inhibition of tyrosinase while mRNA expression of melanogenic enzymes was not affected. In conclusion, we demonstrated that PAL-10 and PAL-12 can be used as a new cosmetic ingredient with strong brightening efficacies. [ABSTRACT FROM AUTHOR]

Chiral imines 1a,b, already synthesized in our laboratory, were converted in good yield by reduction into the corresponding N-benzyl-γ-lactams 2a,b. Desilylation followed by oxidation of the hydroxymethyl functionality gave the N-benzyl-β-amino acids 5a,b in good yield and high purity. Starting from compound 6a, the corresponding β-peptoid dimer 8 was prepared, together with its derivatives 9 and 10, these latter displaying conformational restriction about the peptide bond, as evidenced by NMR data. [ABSTRACT FROM AUTHOR]

Peptide scaffolds are diverse chemical structures providing a major base for drug development. Nature modifies a premature peptide with respect to a basic scaffold structure to create a mature and active peptide. Mimicking the natural scaffolds with desirable modifications i.e., scaffold-hopping will decrease the enormous efforts of chemical syntheses and testing for drug development. We have surveyed the scaffold-based compounds being used for anticancer, antiinfective, antiinflammatory and antidiabetic activities. Synthetic peptidomimetics like aptamers, dendrimers, arylamide foldamers, β peptides, d peptides etc. provide an anticipative picture for the therapeutic use of scaffold structures. Free energy based conformational analysis of peptidomimetics provides details of their structure-activity relationships. Diverse forms of such peptidomimetics with respect to their structure and applications are discussed alongwith the mimetics which reached clinical trials. The review gives an insight into the future panoramas of drug development and identifies few peptide scaffolds having diverse potential with chemical modifications. [ABSTRACT FROM AUTHOR]

Apoptosis is a biological process relevant to human disease states that is strongly regulated through protein–protein complex formation. These complexes represent interesting points of chemical intervention for the development of molecules that could modulate cellular apoptosis. The apoptosome is a holoenzyme multiprotein complex formed by cytochrome c-activated Apaf-1 (apoptotic protease-activating factor), dATP and procaspase-9 that link mitochondria disfunction with activation of the effector caspases and in turn is of interest for the development of apoptotic modulators. In the present study we describe the identification of compounds that inhibit the apoptosome-mediated activation of procaspase-9 from the screening of a diversity-oriented chemical library. The active compounds rescued from the library were chemically optimised to obtain molecules that bind to both recombinant and human endogenous Apaf-1 in a cytochrome c-noncompetitive mechanism that inhibits the recruitment of procaspase-9 by the apoptosome. These newly identified Apaf-1 ligands decrease the apoptotic phenotype in mitochondrial-mediated models of cellular apoptosis.Cell Death and Differentiation (2006) 13, 1523–1532. doi:10.1038/sj.cdd.4401828; published online 9 December 2005 [ABSTRACT FROM AUTHOR]

This report describes a versatile approach in thegeneration of peptidomimetic bead libraries. Themethod is based on the preparation of peptide–peptoidhybrids using the portioning–mixing procedure, whichgives diverse peptidomimetic bead libraries composedof peptides, peptoids and peptide–peptoid hybrids. Weterm these peptomers, from peptide–peptoidhybrid polymers. The synthesis of the peptomersis easily accomplished by adapting the peptoidsynthesis strategy, in which a primary amine reactswith bromoacetic acid, and we combine this methodologywith conventional peptide synthesis. The sequence ofthe active compound is deduced by conventionalmicrosequencing using Edman degradation chemistry,thus avoiding the synthesis of a coding structure orthe addition of molecular tags. We demonstrate theutility of the peptomer approach by the synthesis ofa bead library together with the identification ofnovel peptidomimetic ligands binding to themacromolecular targets streptavidin and the insulin receptor. [ABSTRACT FROM AUTHOR]