Macrocyclic peptides as regulators of protein-protein interactions

Protein-protein interactions are attractive but challenging targets for drug discovery. Recent technological progress and examples using macrocyclic peptides as protein interaction modulators are reviewed.     

Investigating Alanine–Silica Interaction by Means of First‐Principles Molecular‐Dynamics Simulations

In our attempts to achieve a detailed understanding of protein–silica interactions at an atomic level we have, as a first step, simulated a small system consisting of one alanine in different protonation states, and a hydroxylated silica surface, using a first‐principles molecular‐dynamics technique. The simulations are carried out in vacuo as well as in the presence of water molecules. In the case of a negatively charged surface and an alanine cation, an indirect proton transfer from the alanine carboxylic group to the surface takes place. The transfer involves several water molecules revealing an alanine in its zwitterionic state interacting with the neutral surface through indirect hydrogen bonds mediated by water molecules. During the simulation of the zwitterionic state the ammonium group eventually establishes a direct ? N? H???O? Si interaction, suggesting that the surface–amino group interaction is stronger than the interaction between the surface and the carboxylic group. In vacuum simulations, the amino group exhibits clearly stronger interactions with the surface than the carboxylic group.     

Late-Stage Peptide Macrocyclization by Palladium-Catalyzed Site-Selective C−H Olefination of Tryptophan

Transition-metal-catalyzed C−H activation has shown potential in the functionalization of peptides with expanded structural diversity. Herein, the development of late-stage peptide macrocyclization methods by palladium-catalyzed site-selective C(sp²)−H olefination of tryptophan residues at the C2 and C4 positions is reported. This strategy utilizes the peptide backbone as endogenous directing groups and provides access to peptide macrocycles with unique Trp–alkene crosslinks.     

反相高效液相色谱/电喷雾质谱法分析化学合成七肽粗产物

利用RP—HPLC／ESI—MS直接分析用芴甲氧羰基(Fmoc)固相多肽合成方法在PHB树脂上偶联合成的一个七肽(H2N—Tyr—Val—Asn-Thr-Asn—Met—Gly—COOH,Mr797．3)粗产物。RP—HPLC显示合成粗产物含有1个主成分,4个次要成分和多个微量成分;与之联用的电喷雾质谱则同步准确地测定出各成分的分子量(m／z)并自动对各主要成分的化学结构进行了串联质谱分析。结果证明,粗产物中的主成分即为目标七肽,另外几个主要副产物为七肽的氧化产物或残缺肽。     

多肽合成中羧基活化方法的一些新进展

本文简要叙述了多肽合成中的羧基活化问题。重点讨论了作者近年来在此领域所进行的工作,如含氮杂环作为活化羧基的离去基团和几个新的含磷多肽试剂。     

Collagen-like peptides and peptide–polymer conjugates in the design of assembled materials

Collagen is the most abundant protein in mammals, and there has been long-standing interest in understanding and controlling collagen assembly in the design of new materials. Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs) or collagen-related peptides (CRPs), have thus been widely used to elucidate collagen triple helix structure as well as to produce higher-order structures that mimic natural collagen fibers. This mini-review provides an overview of recent progress on these topics, in three broad topical areas. The first focuses on reported developments in deciphering the chemical basis for collagen triple helix stabilization, which we review not with the intent of describing the basic structure and biological function of collagen, but to summarize different pathways for designing collagen-like peptides with high thermostability. Various approaches for producing higher-order structures via CLP self-assembly, via various types of intermolecular interaction, are then discussed. Finally, recent developments in a new area, the production of polymer–CLP bioconjugates, are summarized. Biological applications of collagen contained hydrogels are also included in this section. The topics may serve as a guide for the design of collagen-like peptides and their bioconjugates for targeted application in the biomedical arena.