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For the purpose of seeking new antibiotics, researchers usually modify the already-existing ones. However, this strategy has been extensively used and is close to its limits, especially in the case of aminoglycosides, and it is difficult to find a proper aminoglycoside antibiotic for novel modification. In this paper, we reported the design, synthesis, and evaluation of a series of 5-epi-neamine derivatives based on the structural information of bacterial 16S RNA A-site binding with aminoglycosides. Bioassay results showed that our design strategy was feasible. Our study offers a new way to search for structurally novel aminoglycosides. Meanwhile, our study provides valuable structure-activity relationship information, which will lead to better understanding and exploitation of the drug target, and improved development of new aminoglycoside antibiotics.

Bergenin, which is isolated from Bergenia species, exhibits various pharmacological properties. In the search for new types of immunosuppressants, a series of bergenin derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The experimental data demonstrated that compounds 7 and 13 showed the strongest inhibition effects on mouse splenocyte proliferation (IC(50) = 3.52 and 5.39 μM, respectively). Further studies revealed that the inhibitory effect may come from the suppression of both IFN-γ and IL-4 cytokines. Alkylated derivatives of bergenin with n-hexyl and n-heptyl on the two phenolic hydroxyl groups showed better inhibitory activities. The hydrophobicity of bergenin derivatives, the configuration of the 4-OH in bergenin, and the ability to form hydrogen bonds of the substituents on the C-4 position are important to the immunosuppressive activity. This work proved that the modifications of bergenin may represent a new route to the discovery of a new class of immunosuppressive agents.

O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function. Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels. Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic. Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines. Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification. In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability. Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.

It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N-substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p-tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC50 =2.16 and 2.48 μm, respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j-n) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN-γ and IL-4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold potential as immunosuppressive agents.

A general approach to the synthesis of diverse heteroaryl-C-Δ1,2-glycosides has been developed by employing the Pd(OAc)2/CuI cocatalyzed direct cross-coupling of five-membered nitrogen heterocycles with 1-iodoglycals in a C–H activation manner. Using this method, 27 examples of heteroaryl-C-Δ1,2-glycosides, containing indoles, thiazoles, benzothiazoles, imidazoles, benzimidazoles, and benzoxazoles as aglycones were obtained in 43–99% yield.

A general and efficient approach to the synthesis of various C-acyl glycosides has been developed via Pd2(dba)3/CuTC co-catalyzed cross-coupling reaction of glycosyl carbothioates with arylboronic acids. The reaction showed a broad substrate scope and 25 examples were exhibited in 61%–97% isolated yields. Furthermore, this reaction was applied to the gram-scale preparation of C-acyl glycosides. The coupled products can be further transformed into diverse biologically useful compounds, as exemplified by the synthesis of protected sergliflozin-A mimics.

Since the immunosuppressive agents currently used in clinics have significant side effects, it is very important to search for new effective and safe immunosuppressants. Iminosugars as a new class of immunosuppressants are less explored. In this report, 24 new N-arylated iminosugar derivatives, including d-talo and d-galacto epimers, were designed and synthesized, and their immunosuppressive effects were evaluated by MTT assay. The experimental data demonstrated that compound 20 showed the strongest inhibition effect (IC50 = 6.94 μM). Further studies revealed that the inhibitory effects on splenocyte proliferation may come from the suppression of both IFN-γ and IL-4 cytokines. The preliminary structure-activity relationship (SAR) analysis suggested that N-arylated d-galacto-type iminosugars showed better inhibitory activities than d-talo-type analogues. The SAR analysis also showed that the inhibition effect of iminosugars can be improved by decreasing the polarity or increasing the hydrophobicity. These results may be beneficial to the discovery of new iminosugar derivatives as immunosuppressive agents.

3-Butenyloxycarbonyl (Bloc) has been identified as a new hydroxyl protecting group, which can be introduced under mild conditions in high yields and selectively removed by OsO4/NaIO4/2,6-lutidine in CH3CN–H2O without affecting most commonly-used protecting groups. Moreover, this new protecting group is inert under glycosylation conditions.

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2–6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7–13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.

O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function. Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels. Herein, using in vitro substrate screening, we identified GlcNAcF

Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule dimeric lysine alkylamides as mimics of AMPs. Evaluation of these mimics against a panel of Gram-positive and Gram-negative bacteria including MDR strains was performed, and a broad-spectrum and potent compound 3d was identified. This compound displayed high specificity toward bacteria over mammalian cell. Time-kill kinetics and mechanistic studies suggest that compound 3d quickly eliminated bacteria in a bactericidal mode by disrupting bacterial cell membrane. In addition, lead compound 3d could inhibit biofilm formation and did not develop drug resistance in S. aureus and E. coli over 14 passages. These results suggested that dimeric lysine nonylamide has immense potential as a new type of novel small molecular agent to combat antibiotic resistance.

Novel indolo-quinoline compounds were efficiently prepared via a Povarov-type reaction, and the structures were further modified by a Suzuki coupling reaction. The corresponding BF2-rigidified complexes were prepared and their spectroscopic properties were characterized with large Stokes shifts (up to 211 nm) and up to near-infrared (NIR) wavelength (667 nm). The synthetic complexes could be used as new fluorescent dyes.

An efficient method for the construction of cyclopropane-fused dihydroquinolines was established by a novel Povarov-type three-component reaction of aromatic aldehydes, anilines and cyclopropenes in the presence of trifluoromethanesulfonic acid. The reaction proceeded in a regioselective and diastereoselective manner. Furthermore, the dihy-droquinolines were smoothly converted to benzazepine derivatives via a ring opening/isomerization sequence, further expanding the synthetic scope.

A convenient approach to the synthesis of novel triazole- N -glycoside derivatives was developed via CuSCN-catalyzed click reaction and Ullmann-type coupling reaction for the first time. The SGLT2 inhibitory activities of these synthetic N -glycosides were evaluated, and some compounds showed moderate SGLT2 inhibition activities at 100 nM. The results could benefit the discovery of new SGLT2 inhibitors for the treatment of diabetes.

Crystal engineering of the nbo metal-organic framework (MOF) platform MOF-505 with a custom-designed azamacrocycle ligand (1,4,7,10-tetrazazcyclododecane-N,N',N'',N'''-tetra-p-methylbenzoic acid) leads to a high density of well-oriented Lewis active sites within the cuboctahedral cage in MMCF-2, [Cu2(Cu-tactmb)(H2O)3(NO3)2]. This MOF demonstrates high catalytic activity for the chemical fixation of CO2 into cyclic carbonates at room temperature under 1 atm pressure.

The 3-butenyloxycarbonyl group can be introduced into carbohydrates such as (I) under mild conditions.

A monoselective synthesis of aryl-C-Δ1,2-glycosides from 1-iodoglycals via palladium-catalyzed ortho-C–H activation of N-quinolyl benzamides has been developed. An amino acid derivative was used as a crucial ligand to improve the yield and monoselectivity of the coupling reaction. The utility of this protocol was demonstrated by a concise synthesis of key moieties of some natural products.

A monoselective synthesis of aryl-C-Δ(1,2)-glycosides from 1-iodoglycals via palladium-catalyzed ortho-C-H activation of N-quinolyl benzamides has been developed. An amino acid derivative was used as a crucial ligand to improve the yield and monoselectivity of the coupling reaction. The utility of this protocol was demonstrated by a concise synthesis of key moieties of some natural products.

Although peptide amphiphiles have been explored as nanomaterials for different applications, nanostructures formed by hierarchical molecular assembly of sequence-specific peptidomimetics are much less developed. Such protein-like nanomaterials could enhance the current application of peptide-based amphiphiles by enriching the diversity of nanostructures, increasing in vivo stability for biomedical applications, and facilitating the understanding of biomacromolecular self-assembly. Herein we present a biomimetic γ-AApeptide amphiphile which forms nanorods. Our results demonstrate the capability of γ-AApeptide amphiphiles as a potential scaffold for the preparation of biomimetic and bioinspired nanostructures. The programmability and biocompatibility of γ-AApeptides could lead to novel nanomaterials for a wide variety of applications.

Antimicrobial peptides (AMPs) hold promise to circumvent the emergence of drug resistance occurring in the treatment of bacteria using many conventional antibiotics. Antimicrobial peptidomimetics, which mimic bactericidal mechanisms of AMPs, may overcome the disadvantages of AMPs and become the new generation of antibiotic therapeutics. In this review, some recent examples in the development of antimicrobial peptidomimetics are highlighted. The potential of antimicrobial agents has been demonstrated for therapeutic uses. Meanwhile, perspectives on their further development and applications are also presented.

The solid-phase synthesis of γ-AApeptides using a novel submonomeric approach that utilizes an allyl protection is reported. The strategy successfully circumvents the necessity of preparing γ-AApeptide building blocks in order to prepare γ-AApeptide sequences. This method will maximize the potential of developing chemically diverse γ-AApeptide libraries and thereby facilitate the biological applications of γ-AApeptides in the future.

A convenient synthesis of polyoxygenated tetrahydrothiopyrans and thiepanes from various alditol derivatives with xylo, ribo, manno, gluco, galacto, and fuco configurations is described. The preparation started from the corresponding partially protected alditols and proceeded in a ‘one-pot’ manner to afford the final products in 80%–95% yield. Furthermore, thiosugar compounds 2b, 2d, and 2g were converted to the optically pure polyoxygenated cycloalkenes through Ramberg–Backlund reaction in moderate to good overall yield. The procedures can be used for the preparation of polyoxygenated thiosugars and cycloalkenes on a relatively large scale.

Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a γ-AApeptide mimetic of Tat (48-57) can cross the cell membranes and enter the cytoplasm and nucleus of cells, with efficiency comparable to or better than that of Tat peptide (48-57). Deletion of the four side chains of the γ-AApeptide attenuates translocation capability. We also establish that the γ-AApeptide is even less toxic than the Tat peptide against mammalian cells. In addition to their low toxicity, γ-AApeptides are resistant to protease degradation, which may prove to be advantageous over α-peptides for further development of molecular transporters for intracellular delivery.

Some short and cationic peptides such as the Tat peptide can cross the cell membrane and function as vectors for intracellular delivery. Here we show that an α-AApeptide is able to penetrate the membranes of living cells from an extracellular environment and enter the endosome and cytoplasm of cells. The efficiency of the cellular uptake is comparable to a Tat peptide (48-57) of the same length and is unexpectedly superior to an α-peptide with identical functional groups. The mechanism of uptake is similar to that of the Tat peptide and is through endocytosis by an energy-dependent pathway. Due to the easy synthesis of the α-AApeptides, their resistance to proteolytic hydrolysis, and their low cytotoxicity, α-AApeptides represent a new class of transporters for the delivery of drugs.

An efficient and facile synthesis of phytosphingosine and dihydrosphingosine derivatives is described with less steps and in improved overall yield (66–72%) starting from commercially available tri-O-benzyl-D-galactal. The key steps include Wittig reaction, Mitsunobu transformation, reduction, and deprotection.

An efficient method for the construction of cyclopropane-fused dihydroquinolines was established by a novel Povarov-type three-component reaction of aromatic aldehydes, anilines and cyclopropenes in the presence of trifluoromethanesulfonic acid. The reaction proceeded in a regioselective and diastereoselective manner. Furthermore, the dihy-droquinolines were smoothly converted to benzazepine derivatives via a ring opening/isomerization sequence, further expanding the synthetic scope.

Sialylconjugates on cell surfaces are involved in many biological events such as cellular recognition, signal transduction, and immune response. It has been reported that aberrant sialylation at the nonreducing end of glycoconjugates and overexpression of sialyltransferases (STs) in cells are correlated with the malignance, invasion, and metastasis of tumors. Therefore, inhibitors of STs would provide valuable leads for the discovery of antitumor drugs. On the basis of the transition state of the enzyme-catalyzed sialylation reaction, we proposed that the cyclopentane skeleton in its two puckered conformations might mimic the planar structure of the donor (CMP-Neu5Ac) in the transition state. A series of cyclopentane-containing compounds were designed and synthesized by coupling different cyclopentane α-hydroxyphosphonates with cytidine phosphoramidite. Their inhibitory activities against recombinant human ST6Gal-I were assayed, and a potent inhibitor 48l with a Ki of 0.028 ± 0.006 μM was identified. The results show that the cyclopentanoid-type compounds could become a new type of sialyltransferase inhibitors as biological probes or drug leads.

The creation and development of nonnatural peptidomimetics has become an area of increasing significance in bioorganic and chemical biology. A wide range of new peptide mimics with novel structures and functions are urgently needed to be explored in order to identify potential drug candidates and targeted probes, and to study protein functions. AApeptides are a new class of peptide mimics based on chiral PNA backbone. They are resistant to proteolytic degradation and have limitless potential for diversification. They have been found to have a wide variety of biological applications including cellular translocation, disruption of protein-protein interactions, formation of nanostructures, antimicrobial activity, etc. The synthesis of AApeptides is modular and straightforward. In this chapter, methods for the synthesis of AApeptides (including different subclasses) are described.

We report the design, synthesis, characterization and evaluation of a novel class of γ-AApeptide one-bead-one-compound (OBOC) library, from which a small γ-AApeptide was identified to effectively prevent and disassemble Aβ aggregation.

The creation and development of nonnatural peptidomimetics has become an area of increasing significance in bioorganic and chemical biology. A wide range of new peptide mimics with novel structures and functions are urgently needed to be explored in order to identify potential drug candidates and targeted probes, and to study protein functions. AApeptides are a new class of peptide mimics based on chiral PNA backbone. They are resistant to proteolytic degradation and have limitless potential for diversification. They have been found to have a wide variety of biological applications including cellular translocation, disruption of protein-protein interactions, formation of nanostructures, antimicrobial activity, etc. The synthesis of AApeptides is modular and straightforward. In this chapter, methods for the synthesis of AApeptides (including different subclasses) are described.

Antibiotic resistance is an increasing public health concern around the world, and is recognized as one of the greatest threats facing humankind in the 21st century. Natural antimicrobial peptides (AMPs) are small cationic amphiphilic peptides found in virtually all living organisms, and play a key role in the defense against bacterial infections. Compared with conventional antibiotics, which target specific metabolic processes, AMPs are able to adopt globally amphipathic conformations, and kill bacteria through disruption of their membranes. As such, AMPs do not readily induce drug-resistance. However, AMPs are associated with intrinsic drawbacks such as low-to-moderate activity, susceptibility to enzymatic degradation, and inconvenience for optimization. Recently, we have developed a new class of peptidomimetics termed “AApeptides”. Such peptide mimics are highly resistant to protease degradation and are straightforward for chemical diversification and development. Our current studies show that AApeptides with globally amphipathic structures can mimic the bactericidal mechanism of AMPs, and display potent and broad-spectrum activity against both Gram-positive and -negative multi-drug-resistant bacteria. In this review, we summarize our current findings of antimicrobial AApeptides, and discuss potential future directions on the development of more potent and specific analogues.

The patent application WO201268820 claims a new class of polymyxin derivatives with potent antibacterial activity, especially toward Gram-negative pathogens. Compared to parent polymyxin B (PMB), the new derivatives have more potent antibacterial activity, as well as reduced cytotoxicity against human renal cells.

The creation and development of nonnatural peptidomimetics has become an area of increasing significance in bioorganic and chemical biology. A wide range of new peptide mimics with novel structures and functions are urgently needed to be explored in order to identify potential drug candidates and targeted probes, and to study protein functions. AApeptides are a new class of peptide mimics based on chiral PNA backbone. They are resistant to proteolytic degradation and have limitless potential for diversification. They have been found to have a wide variety of biological applications including cellular translocation, disruption of protein-protein interactions, formation of nanostructures, antimicrobial activity, etc. The synthesis of AApeptides is modular and straightforward. In this chapter, methods for the synthesis of AApeptides (including different subclasses) are described.

There is increasing demand to develop antimicrobial peptides (AMPs) as next generation antibiotic agents, as they have the potential to circumvent emerging drug resistance against conventional antibiotic treatments. Non-natural antimicrobial peptidomimetics are an ideal example of this, as they have significant potency and in vivo stability. Here we report for the first time the design of lipidated γ-AApeptides as antimicrobial agents. These lipo-γ-AApeptides show potent broad-spectrum activities against fungi and a series of Gram-positive and Gram-negative bacteria, including clinically relevant pathogens that are resistant to most antibiotics. We have analyzed their structure-function relationship and antimicrobial mechanisms using membrane depolarization and fluorescent microscopy assays. Introduction of unsaturated lipid chain significantly decreases hemolytic activity and thereby increases the selectivity. Furthermore, a representative lipo-γ-AApeptide did not induce drug resistance in S. aureus, even after 17 rounds of passaging. These results suggest that the lipo-γ-AApeptides have bactericidal mechanisms analogous to those of AMPs and have strong potential as a new class of novel antibiotic therapeutics.

In human physiology, proteins at all times are synthesized, processed, degraded and posttranslationally modified to varying degrees and at different rates, for their participations in a wide variety of activities to maintain normal functions of the body (Murray et al. 2007). In the successful proceedings of all the biological events, signals are consistently received and sent via physical contacts between proteins (Murray et al. 2007). The communication between proteins or the alternatively called non-covalent protein-protein interactions are thereby considered as important as proteins’ own functions (Murray et al. 2007). Disruptions of these signaling pathways by either mutational changes or deregulation of one of the protein partners would result in a series of diseases (Murray et al. 2007). On the other hand, therapeutic approaches based on chemical agents could potentially inhibit protein-protein interactions, thereby restoring the balance of signaling pathways, and leading to the cure of diseases (Murray et al. 2007). However, it is quite challenging to develop chemical agents which can target protein-protein interactions (Arkin et al. 2004; Whitty et al. 2006). Unlike the traditional medicinal chemistry approach, in which small molecule inhibitors are developed to target the hydrophobic pocket of enzymes / kinases, chemical agents are now required to bind to large surfaces of proteins that are usually amphiphilic and flexible (Murray et al. 2007). Yet a number of successful stories have been reported (Murray et al. 2007). Taking the p53/MDM2 system as an example, the p53/MDM2 has been a model system for the inhibition of protein-protein interactions, and has been reported to be the targets of a wide variety of inhibitors (Oren 1999; Balint et al. 2001; McLure et al. 2004; Brooks et al. 2006).

We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance.

Traditional dendrimers possess unique cascade-branched structural properties that allow for multivalent modifications with drug cargos, targeting/delivery agents and imaging tools. In addition to multivalency, the dendrimer's macromolecular size also brings about the enhanced permeability and retention (EPR) effect, which makes it an attracting agent for drug delivery and biosensing. Similar to other macromolecules, therapeutic application of dendrimers in the human body faces practical challenges such as target specificity and toxicity. The latter represents a substantial issue due to the dendrimer's unnatural chemical structure and relatively large size, which prohibit its in vivo degradation and excretion from the body. To date, a class of self-immolative dendrimers has been developed to overcome these obstacles, which takes advantage of its unique structural backbone to allow for cascade decompositions upon a simple triggering event. The specific drug release can be achieved through a careful design of the trigger, and as a result of the fragmentation, the generated small molecules are either biodegradable or easily excreted from the body. Though still at a preliminary stage, the development of this novel approach represents an important direction in nanoparticle-mediated drug delivery and sensor design, thereby opening up an insightful frontier of dendrimer based applications.

The interactions between proteins and RNAs are of vital importance for many cellular processes, including transcription and processing of RNA, translation, and viral infections. Here we report an γ-AApeptide that can mimic HIV-1 Tat protein and bind to TAR RNAs of HIV and BIV with nanomolar affinity, comparable to that of the RNA-binding fragment of Tat (amino acids 49–58). The interaction is resistant to the presence of a large excess of tRNA. With resistance to proteolytic hydrolysis and limitless potential for diversification, γ-AApeptides may emerge as a new class of peptidomimetics to modulate RNA-protein interactions.

Besides the common issue of drug-resistance, the conventional approaches for cancer diagnostics and treatment are constantly challenged by poor selectivity and limited access to neoplastic cells, which not only lead to the dose-limiting effect on the tumor region, but also bring side-effects to healthy cells/tissues. In recent years, a novel strategy has arisen to target the vasculature of tumors for drug-delivery and molecular imaging, based on the success of anti-angiogenic therapy. In addition to being easily accessible, the endothelial cells of tumor vasculature are also genetically stable and thus do not develop drug-resistance, making them ideal targets for chemotherapeutics and biomedical imaging. Among various ligands identified so far, the Asn-Gly-Arg (NGR) tripeptide can specifically target the neovasculature via interaction with the aminopeptidase N (APN/CD13) receptor which is highly up-regulated in the membranes of endothelial tumor cells. NGR-directed drug delivery as well as molecular imaging have therefore been undergone development, and appear to be intriguing approaches in current cancer research. Herein we highlight some recent developments of the NGR peptide based cancer therapy including drug-delivery and imaging studies, with future perspectives. Some of these agents have been under clinical trials, indicating promising future for the NGR-based drugs.

NaHSO 4 ·SiO 2 was used as an efficient heterogeneous catalyst for both the formation and the cleavage of benzylidene -acetals. This catalyst is compatible with many functional or protective groups. Under different solvent systems, either the formation or the cleavage of benzylidene acetals was carried out smoothly in -excellent yields and with good chemoselectivity.

Antibiotic resistance is an increasing public health concern around the world, and is recognized as one of the greatest threats facing humankind in the 21(st) century. Natural antimicrobial peptides (AMPs) are small cationic amphiphilic peptides found in virtually all living organisms, and play a key role in the defense against bacterial infections. Compared with conventional antibiotics, which target specific metabolic processes, AMPs are able to adopt globally amphipathic conformations, and kill bacteria through disruption of their membranes. As such, AMPs do not readily induce drug-resistance. However, AMPs are associated with intrinsic drawbacks such as low-to-moderate activity, susceptibility to enzymatic degradation, and inconvenience for optimization. Recently, we have developed a new class of peptidomimetics termed "AApeptides". Such peptide mimics are highly resistant to protease degradation and are straightforward for chemical diversification and development. Our current studies show that AApeptides with globally amphipathic structures can mimic the bactericidal mechanism of AMPs, and display potent and broad-spectrum activity against both Gram-positive and -negative multi-drug-resistant bacteria. In this review, we summarize our current findings of antimicrobial AApeptides, and discuss potential future directions on the development of more potent and specific analogues.

Antimicrobial drug resistance is one of the greatest threats facing mankind. Antimicrobial peptides (AMPs) can potentially circumvent drug resistance, probably through a bacterial membrane-disruption mechanism. However, they suffer from low in vivo stability, potential immunogenicity, and difficulty in optimization. The development of antimicrobial peptidomimetics is therefore an emerging research area as they avoid the potential disadvantages of AMPs. Cyclic peptidomimetics are of significant interest since constraints induced by cyclization are expected to further improve their antimicrobial activity. Nonetheless, the report of cyclic oligomeric peptidomimetics for antimicrobial development is rare. Herein, for the first time, we report the design and synthesis of cyclic γ-AApeptides via an on-resin cyclization. These cyclic γ-AApeptides are potent and broad-spectrum active against fungus and multi-drug resistant Gram-positive and Gram-negative bacterial pathogens. Our results demonstrate the potential of cyclic γ-AApeptides as a new class of antibiotics to circumvent drug resistance by mimicking the bactericidal mechanism of AMPs. Meanwhile, the facile synthesis of cyclic γ-AApeptides may further expand the applications of γ-AApeptides in biomedical sciences.

A γ-AApeptide-based tracer for positron emission tomography imaging of integrin α(v)β(3) is reported. Despite its shorter sequence and linear nature, this tracer had comparable integrin α(v)β(3) binding affinity to the cyclic arginine-glycine-aspartic acid peptide but significantly higher resistance to enzymatic degradation and better stability.

A two-fold interpenetrating microporous metal–organic framework, MMCF-1, has been constructed via the self-assembly of a custom-designed macrocyclic tetracarboxylate ligand and Cd(II), and it exhibits interesting selective uptake of CO2 over N2.

A new class of peptide mimics termed “γ-AApeptides” has been described. The design and synthesis of γ-AApeptides, and potential bioactivities towards p53/MDM2 interaction were demonstrated. γ-AApeptides were also found to be highly resistant to proteolysis. The development of sequence-specific γ-AApeptides may lead to a family of peptidomimetics with a new framework for drug discovery or peptide/protein mimicry.