Dynamic covalent chemistry enables formation of antimicrobial peptide quaternary assemblies in a completely abiotic manner
Dynamic covalent chemistry enables formation of antimicrobial peptide quaternary assemblies in a completely abiotic manner
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DOI：
10.1038/nchem.2847
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发表时间：
2018-01-01
期刊：
影响因子：
21.8
通讯作者：
Anslyn, Eric V.
中科院分区：
文献类型：
--
作者：
Reuther, James F.;Dees, Justine L.;Anslyn, Eric V.
Naturally occurring peptides and proteins often use dynamic disulfide bonds to impart defined tertiary/quaternary structures for the formation of binding pockets with uniform size and function. Although peptide synthesis and modification are well established, controlling quaternary structure formation remains a significant challenge. Here, we report the facile incorporation of aryl aldehyde and acyl hydrazide functionalities into peptide oligomers via solid-phase copper-catalysed azide-alkyne cycloaddition (SP-CuAAC) click reactions. When mixed, these complementary functional groups rapidly react in aqueous media at neutral pH to form peptide-peptide intermolecular macrocycles with highly tunable ring sizes. Moreover, sequence-specific figure-of-eight, dumbbell-shaped, zipper-like and multi-loop quaternary structures were formed selectively. Controlling the proportions of reacting peptides with mismatched numbers of complementary reactive groups results in the formation of higher-molecular-weight sequence-defined ladder polymers. This also amplified antimicrobial effectiveness in select cases. This strategy represents a general approach to the creation of complex abiotic peptide quaternary structures.
