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Synthetic therapeutic peptides are a complex and popular class of pharmaceuticals. In recent years, peptides with proven therapeutic activity have gained significant interest in the market. The determination of synthetic peptide enantiomeric purity plays a critical role in the evaluation of the quality of the medicine. Since racemization is one of the most common side reactions occurring in AAs or peptides, enantiomeric impurities such as D‐isomers can form during the peptide synthesis or can be introduced from the starting materials (e.g., AAs). The therapeutic effect of a synthetic or semi‐synthetic bioactive peptide molecule depends on its AA enantiomeric purity and secondary/tertiary structure. Therefore, the enantiomeric purity determination for synthetic peptides is supportive for interpreting unwanted therapeutic effects and determining the quality of synthetic peptide therapeutics. However, enantiomeric purity analysis encounters formidable analytical challenges during chromatographic separation, as D/L isomers have identical physical–chemical properties except stereochemical configuration. To ensure peptides AA stereochemical configuration whether in the free or bound state, sensitive and reproducible quantitative analytical method is mandatory. In this regard, numerous analytical techniques were emerged for the quantification of D‐isomeric impurities in synthetic peptides, but still, very few reports are available in the literature. Thus, the purpose of this paper is to provide an overview of the importance, regulatory requirements, and various analytical methods used for peptide enantiomeric purity determination. In addition, we discussed the available literature in terms of enantiomeric impurity detection, common hydrolysis procedural aspects, and different analytical strategies used for sample preparation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are a significant and growing burden on global health services, and it is now accepted that impairment of vascular function represents a major preliminary step in the development of CVD. There is considerable interest in identifying both causal factors of impaired vascular function, as well as related nutritional factors that may lower the risk of developing CVD, and food‐derived bioactive peptides and amino acids have emerged as one such area. Dairy foods contain two groups of proteins, whey proteins and caseins, which represent a rich source of bioactive peptides that are released during food processing and/or digestion. These peptides have a number of physiological activities including the potential to reduce blood pressure. Research, including acute and longer‐term randomised controlled trials, animal models and in vitro models has demonstrated the potential impact of dairy proteins on vascular function. The purpose of this paper is to narratively review the evidence, primarily from randomised controlled trials, examining the effects of whey proteins, their peptides and amino acids on vascular function and related issues including blood pressure. In addition, it will explore the potential underlying mechanisms responsible for these effects. It concludes that there is increasing evidence that whey proteins, and notably the bioactive peptides and amino acids released during their digestion, can have beneficial effects on aspects of vascular function and thus contribute to CVD risk reduction. It also highlights a number of beneficial effects of whey proteins including those on blood pressure, arterial stiffness, nitric oxide production and inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The MHC‐peptide interaction has a subtle influence on host resistance to virus. This paper aims to study the relationship between MHC‐peptide interaction and MHC‐related virus‐resistance. Methods: By 3D homology modeling, the structure of chicken BF2 molecule BF2*0201 (PDB code: 4d0d) was studied and compared with the known structures of BF2 molecule BF2*0401 (PDB code: 4e0r) to elucidate the characteristics of BF2*0201‐binding antigenic peptides. Results: The results show that due to the amino acid difference between the two binding groove of 4e0r and 4d0d, the size of the binding groove of the two are 1130 ų and1380 ų respectively, indicating the amino acid species that 4e0r binding peptide has lower selectivity than 4d0d; and because of large side chain conformation of Arg (especially Arg111) of 4e0r replaced by small side chain Tyr111 of 4d0d, the volume of central part of the binding groove of 4d0d is obviously larger than that of 4e0r, indicating that the restrictive of binding antigenic peptides for 4d0d is narrower than that of 4e0r; and on account of the chargeability of the binding groove of the two are different, namely the binding groove chargeability of 4e0r (strong positive polarity) and 4d0d (weak negative polarity). Conclusion: There are generally more peptides presented by the BF2 of B2 haplotype than by that of B4 haplotype, leading to more resistance of B2 than that of B4 to virus. [ABSTRACT FROM AUTHOR]

Recently, we presented a strategy for packaging peptides as side‐chains in high‐density brush polymers. For this globular protein‐like polymer (PLP) formulation, therapeutic peptides were shown to resist proteolytic degradation, enter cells efficiently and maintain biological function. In this paper, we establish the role charge plays in dictating the cellular uptake of these peptide formulations, finding that peptides with a net positive charge will enter cells when polymerized, while those formed from anionic or neutral peptides remain outside of cells. Given these findings, we explored whether cellular uptake could be selectively induced by a stimulus. In our design, a cationic peptide is appended to a sequence of charge‐neutralizing anionic amino acids through stimuli‐responsive cleavable linkers. As a proof‐of‐concept study, we tested this strategy with two different classes of stimuli, exogenous UV light and an enzyme (a matrix metalloproteinase) associated with the inflammatory response. The key finding is that these materials enter cells only when acted upon by the stimulus. This approach makes it possible to achieve delivery of the polymers, therapeutic peptides or an appended cargo into cells in response to an appropriate stimulus. [ABSTRACT FROM AUTHOR]

The alteration of amino acid register in peptides could affect their folding properties and thus functions. The effect of sequence in metal ion induced folding of peptide/protein is important in the design of new functional protein structures, such as biomimetics. In this paper, a set of hairpin peptides with identical composition but different histidine locations have been designed to exploit the metal ion‐mediated peptide intramolecular folding transformation through the adjustment of histidine and lysine residue locations. The results demonstrated that the histidine positions in peptide sequence could dramatically affect the coordination modes between peptides and Cu(II) ion. The Cu(II) coordination could affect the secondary structure transformation and self‐assembly along with electrostatic interaction and hydrogen bonding synergistically. Three molecules with VHVH sequence at each side of the turn segment (VDPPT) were apt to coordinate with Cu(II) ion with three or four histidines. The closer the VHVH motifs were to the turn segment, the more easier the molecules were to form β sheet structure with the promotion of Cu(II) ions. These results demonstrated that the purposeful location of key amino acids in peptides could achieve the controllable conformation transformation of hairpin peptides, which provides useful strategies for biomimetic design, such as metalloenzymes. [ABSTRACT FROM AUTHOR]

Herein we provide a guide for adapting the tools developed for protein X-ray crystallography to study the structures and supramolecular assembly of peptides. Peptide crystallography involves selecting a suitable peptide, crystallizing the peptide, collecting X-ray diffraction data, processing the diffraction data, determining the crystallographic phases and generating an electron density map, building and refining models, and depositing the crystallographic structure in the Protein Data Bank (PDB). Advances in technology make this process easy for a newcomer to adopt. This paper describes techniques for determining the X-ray crystallographic structures of peptides: incorporation of amino acids containing heavy atoms for crystallographic phase determination, commercially available kits to crystallize peptides, modern techniques for X-ray crystallographic data collection, and free user-friendly software for data processing and producing a crystallographic structure. [ABSTRACT FROM AUTHOR]

This review summarizes the recent advances in the analysis of amino acids, peptides, and proteins using hydrophilic interaction chromatography. Various reports demonstrate the successful analysis of amino acids under such conditions. However, a baseline resolution of the 20 natural amino acids has not yet been published and for this reason, there is often a need to use mass spectrometry for detection to further improve selectivity. Hydrophilic interaction chromatography is also recognized as a powerful technique for peptide analysis, and there are a lot of papers showing its applicability for proteomic applications (peptide mapping). It is expected that its use for peptide mapping will continue to grow in the future, particularly because this analytical strategy can be combined with reversed-phase liquid chromatography, in a two-dimensional setup, to reach very high resolving power. Finally, the interest in hydrophilic interaction chromatography for intact proteins analysis is less evident due to possible solubility issues and a lack of suitable hydrophilic interaction chromatography stationary phases. To date, it has been successfully employed only for the characterization of membrane proteins, histones, and the separation of glycosylated isoforms of an intact glycoprotein. From our point of view, the number of hydrophilic interaction chromatography columns compatible with intact proteins (higher upper temperature limit, large pore size, etc.) is still too limited. [ABSTRACT FROM AUTHOR]

Increasing numbers of biological applications of fullerenyl amino acids and their derivatives encouraged us to synthesise [60]fullerenyldihydropyrrole peptides, prepared from the coupling of mono- and bis[60]fullerenyldihydropyrrolecarboxylic acids 4, 5 and 41 with presynthesised peptides 13, 16, 24, 28, 29 and 46. The resulting hydrophobic scaffolded di- and tetra-cationic derivatives were tested against Staphylococcus aureus NCTC 6571 and Escherichia coli NCTC 10418. The synthesis, characterisation and biological results are discussed in this paper. [ABSTRACT FROM AUTHOR]

This paper describes an efficient procedure for the synthesis of micromide, a natural product that shows anti-solid-tumor activity. Our strategy involved the synthesis of N-nosyl-protected amino acids and their N-methylation with iodomethane. The hindered oligopeptides containing N-methyl amino acids were synthesized in excellent yields and high purities. [ABSTRACT FROM AUTHOR]

A water ‐ soluble cyclic hexapeptide comprising an alternate sequence of biphenyl ‐ cored ζ ‐ amino acids and proteinogenic α ‐ amino acids such as l ‐ leucine has been developed. The amino acids were connected by typical peptide synthesis, and the resultant linear hexapeptide was intramolecularly cyclized to form the target cyclic peptide. Theoretical and NMR spectroscopic analyses suggested that the cyclic peptide was folded into an unsymmetrical conformation, and the structure was likely to be flexible. Furthermore, the cyclic peptide became soluble in water by introducing three carboxylate groups. More information can be found in the Full Paper by Mitsuhiko Shionoya et al. on page   1087 in Issue 10, 2017 (DOI: 10.1002/asia.201700203). [ABSTRACT FROM AUTHOR]

An abstract of the paper "Synthesis and Conformational Study of Novel Pyrazine-Based Pseudopeptides Bearing Amidoxime, Amidoxime Ester and 1,2,4-Oxadiazole Units" is presented.

An abstract of the paper " The N-Hydroxymethyl Group as a Traceless Activating Group for the CAL-B-Catalyzed Ring Cleavage of ß-Lactams: A Type of Two-Step Cascade Reaction" is presented.

The Inside Back Cover picture shows palladium‐catalyzed derivatisations of halogenated phenylalanine and tryptophan and dipeptide substrates containing these entities in view of the optimization of lead peptide ligands for improved receptor interactions. A wide scope of substrates is presented to highlight the tolerated peptide functionality during the application of the Suzuki‐Miyaura reaction in aqueous media. In their Full Paper, T. Willemse et al. investigate the influence of unprotected peptide functionalities on the progress of the Pd‐catalyzed reaction. In the background, the collaboration between the Maes and Ballet laboratories is emphasized by the skylines of Antwerp and Brussels. The article highlighted by this cover can be found on p. 2055 ff. of Issue 14, 2015. [ABSTRACT FROM AUTHOR]