Gable Alice, Pohjolainen Emmi, Groenhof Gerrit, Cougnon Fabien B L
Department of Chemistry, Nanoscience Center, University of Jyväskylä, Survontie 9 C, Jyväskylä, 40014, Finland.
Chemistry. 2025 Jun 23;31(35):e202501298. doi: 10.1002/chem.202501298. Epub 2025 May 19.
Naturally occurring peptides are almost exclusively composed of L-amino acids, and the incorporation of D-amino acids can profoundly alter their ability to fold and self-assemble. Here we explore the effects of chirality on the formation of disulfide dynamic combinatorial libraries (DCLs) generated by short cysteine-rich peptides. Our findings consistently show that heterochiral tripeptides form more diverse DCLs than their homochiral counterparts. The most complex library appears to encompass all possible cyclic species up to 19mers. Given that each of these species exists as a mixture of parallel and antiparallel isomers, we estimate this library to contain a total of 2,045 distinct compounds-a remarkable result considering that the library generated by the analogous homochiral peptide predominantly contains two dimers. In certain situations, peptide chirality also affects the relative stability of parallel and antiparallel isomers. Taken together, these results show that small changes in peptide chirality can be dramatically amplified through the formation of cyclic species.
天然存在的肽几乎完全由L-氨基酸组成，而D-氨基酸的掺入可深刻改变其折叠和自组装能力。在此，我们探讨了手性对由富含半胱氨酸的短肽生成的二硫键动态组合库（DCL）形成的影响。我们的研究结果一致表明，异手性三肽比同手性对应物形成更多样化的DCL。最复杂的库似乎包含了所有可能的环状物种，直至19聚体。鉴于这些物种中的每一个都以平行和反平行异构体的混合物形式存在，我们估计这个库总共包含2045种不同的化合物——考虑到由类似的同手性肽生成的库主要包含两种二聚体，这是一个显著的结果。在某些情况下，肽的手性也会影响平行和反平行异构体的相对稳定性。综上所述，这些结果表明，肽手性的微小变化可通过环状物种的形成而被显著放大。
