共查询到20条相似文献,搜索用时 15 毫秒
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Varsha J. Thombare Craig A. Hutton 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(15):5052-5056
Peptide macrocyclization is often a slow process, plagued by epimerization and cyclodimerization. Herein, we describe a new method for peptide macrocyclization employing the AgI‐promoted transformation of peptide thioamides. The AgI has a dual function: chemoselectively activating the thioamide and tethering the N‐terminal thioamide to the C‐terminal carboxylate. Extrusion of Ag2S generates an isoimide intermediate, which undergoes acyl transfer to generate the native cyclic peptide, resulting in a rapid, traceless macrocylization process. Cyclic peptides are furnished in high yields within 1 hour, free of epimerization and cyclodimerization. 相似文献
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Mor Ben-Lulu Eden Gaster Anna Libman Prof. Dr. Doron Pappo 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(12):4865-4869
Biaryl-bridged cyclic peptides comprise an intriguing class of structurally diverse natural products with significant biological activity. Especially noteworthy are the antibiotics arylomycin and its synthetic analogue G0775, which exhibits potent activity against Gram-negative bacteria. Herein, we present a simple, flexible, and reliable strategy based on activating-group-assisted catalytic oxidative coupling for assembling biaryl-bridged cyclic peptides from natural amino acids. The synthetic approach was utilized for preparing a number of natural and unnatural biaryl-bridged cyclic peptides, including arylomycin/G0775 and RP 66453 cyclic cores. 相似文献
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Qian Qu Shuai Gao Fangming Wu Meng-Ge Zhang Ying Li Long-Hua Zhang Dr. Donald Bierer Prof. Chang-Lin Tian Prof. Ji-Shen Zheng Prof. Dr. Lei Liu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(15):6093-6101
The use of synthetic bridges as surrogates for disulfide bonds has emerged as a practical strategy to obviate the poor stability of some disulfide-containing peptides. However, peptides incorporating large-span synthetic bridges are still beyond the reach of existing methods. Herein, we report a native chemical ligation (NCL)-assisted diaminodiacid (DADA) strategy that enables the robust generation of disulfide surrogate peptides incorporating surrogate bridges up to 50 amino acids in length. This strategy provides access to some highly desirable but otherwise impossible-to-obtain disulfide surrogates of bioactive peptide. The bioactivities and structures of the synthetic disulfide surrogates were verified by voltage clamp assays, NMR, and X-ray crystallography; and stability studies established that the disulfide replacements effectively overcame the problems of disulfide reduction and scrambling that often plague these pharmacologically important peptides. 相似文献
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Yizhen Yin Qianran Fei Weidong Liu Zhuoru Li Hiroaki Suga Chuanliu Wu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(15):4934-4939
Bicyclic and tricyclic peptides have emerged as promising candidates for the development of protein binders and new therapeutics. However, convenient and efficient strategies that can generate topologically controlled bicyclic and tricyclic peptide scaffolds from fully‐unprotected peptides are still much in demand, particularly for those amenable to the design of biosynthetic libraries. In this work, we report a reliable chemical and ribosomal synthesis of topologically controlled bicyclic and tricyclic peptide scaffolds. Our strategy involves the combination of selenoether cyclization followed by disulfide or thioether cyclization, yielding desirable bicyclic and tricyclic peptides. This work thus lays the foundation for developing peptide libraries with controlled topology of multicyclic scaffolds for in vitro display techniques. 相似文献
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Yftah Tal‐Gan Monika Ivancic Gabriel Cornilescu Tian Yang Helen E. Blackwell 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(31):9059-9063
Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP‐III) signal that can inhibit AgrC‐type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide‐linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS. 相似文献
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Andrea Pizzi Haxel Lionel Ozores Martín Calvelo Rebeca García‐Fandio Manuel Amorín Nicola Demitri Giancarlo Terraneo Silvia Bracco Angiolina Comotti Piero Sozzani Charl X. Bezuidenhout Pierangelo Metrangolo Juan R. Granja 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(41):14614-14618
A cyclic hexapeptide with three pyridyl moieties connected to its backbone forms a hydrogen‐bonded dimer, which tightly encapsulates a single xenon atom, like a pearl in its shell. The dimer imprints its shape and symmetry to the captured xenon atom, as demonstrated by 129Xe NMR spectroscopy, single‐crystal X‐ray diffraction, and computational studies. The dimers self‐assemble hierarchically into tubular structures to form a porous supramolecular architecture, whose cavities are filled by small molecules and gases. 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2017,129(6):1547-1551
Therapeutic applications of peptides are currently limited by their proteolytic instability and impermeability to the cell membrane. A general, reversible bicyclization strategy is now reported to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell‐penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell‐permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell‐permeable bicyclic peptidyl inhibitor against the NEMO‐IKK interaction. 相似文献
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Huy N. Hoang Chongyang Wu Timothy A. Hill Aline Dantas de Araujo Paul V. Bernhardt Ligong Liu David P. Fairlie 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(52):19049-19053
The introduction of an amide bond linking side chains of the first and fifth amino acids forms a cyclic pentapeptide that optimally stabilizes the smallest known α‐helix in water. The origin of the stabilization is unclear. The observed dependence of α‐helicity on the solvent and cyclization linker led us to discover a novel long‐range n to π* interaction between a main‐chain amide oxygen and a uniquely positioned carbonyl group in the linker of cyclic pentapeptides. CD and NMR spectra, NMR and X‐ray structures, modelling, and MD simulations reveal that this first example of a synthetically incorporated long‐range n to π* CO???Cγ=Ο interaction uniquely enforces an almost perfect and remarkably stable peptide α‐helix in water but not in DMSO. This unusual interaction with a covalent amide bond outside the helical backbone suggests new approaches to synthetically stabilize peptide structures in water. 相似文献
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Ekaterina Y. Melikhova Robert D. C. Pullin Christian Winter Timothy J. Donohoe 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2016,128(33):9905-9909
The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp‐2‐CO2H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material. 相似文献
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Huaimin Wang Zhaoqianqi Feng Bing Xu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(31):10532-10541
Using peptide assemblies with emergent properties to achieve elaborate functions has attracted increasing attention in recent years. Besides tailoring the self‐assembly of peptides in vitro, peptide research is advancing into a new and exciting frontier: the rational design of peptide assemblies (or their derivatives) for biological functions in a complex environment. This Minireview highlights recent developments in peptide assemblies and their applications in biological systems. After introducing the unique merits of peptide assemblies, we discuss the recent progress in designing peptides (or peptide derivatives) for self‐assembly with conformational control. Then, we describe biological functions of peptide assemblies, with an emphasis on approach‐instructed assembly for spatiotemporal control of peptide assemblies, in the cellular context. Finally, we discuss the future promises and challenges of this exciting area of chemistry. 相似文献
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Gu HE Li GUO Li Fang MA 《中国化学快报》2006,17(3):289-292
Dendrimers are known for their well-defined, regular, highly branched architectures with a large number of functional groups1. Recently, dendrimers have been widely researched in different fields, such as molecular light havesting, catalysts, liquid cryst… 相似文献
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《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2018,130(21):6258-6262
A broadly applicable chemical cleavage methodology to facilitate MS/MS sequencing was developed for macrocyclic and lasso peptides, which hold promise as exciting new therapeutics. Existing methods such as Edman degradation, CNBr cleavage, and enzymatic digestion are either limited in scope or completely fail in cleavage of constrained nonribosomal peptides. Importantly, the new method was utilized for synthesizing a unique peptide‐based rotaxane (both cyclic and threaded) from the lasso peptide, benenodin‐1 ΔC5. 相似文献
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Anaïs F. M. Noisier Magnus J. Johansson Laurent Knerr Martin A. Hayes William J. Drury Eric Valeur Lara R. Malins Ranganath Gopalakrishnan 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(52):19272-19278
The late‐stage functionalization (LSF) of peptides represents a valuable strategy for the design of potent peptide pharmaceuticals by enabling rapid exploration of chemical diversity and offering novel opportunities for peptide conjugation. While the C(sp2)?H activation of tryptophan (Trp) is well documented, the resurgence of radical chemistry is opening new avenues for the C?H functionalization of other aromatic side‐chains. Herein, we report the first example of LSF at C2 of histidine (His) utilizing a broad scope of aliphatic sulfinate salts as radical precursors. In this work, the exquisite selectivity for histidine functionalization was demonstrated through the alkylation of complex unprotected peptides in aqueous media. Finally, this methodology was extended for the installation of a ketone handle, providing an unprecedented anchor for selective oxime/hydrazone conjugation at histidine. 相似文献
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在有机溶剂中进行酶催化合成肽及肽类衍生物的研究进展 总被引:2,自引:0,他引:2
介绍了有机溶剂中含非天然组分的肽及肽类衍生物的酶催化反应,同时对研究有机溶剂中酶的活性与结构关系的谱学技术进行了评述. 相似文献