Hu Kuan, Sun Chengjie, Li Zigang
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, Guangdong 518055, China.
Bioconjug Chem. 2017 Jul 19;28(7):2001-2007. doi: 10.1021/acs.bioconjchem.7b00321. Epub 2017 Jul 6.
Modification of the cross-linker of constrained peptides has recently received considerable attention. Here, we present a versatile approach to modifing the cross-linking tether of chiral-center-induced helical (CIH) peptides via the S-alkylation reaction. The alkylation process displayed high conversion efficiency, selectivity, and substrate tolerance. Notably, although on-tether S-alkylation could lead to a pair of peptide epimers, the major alkylated product retained the helical structure of its helical precursor peptide. This S-alkylation was readily reversible under reductive conditions, which provides a simple method for traceless modification. In addition to expanding the chemical space of CIH peptides, this strategy is the first on-tether modification platform with known retention of the peptides' original helicity.
近年来，受限肽交联剂的修饰受到了广泛关注。在此，我们提出了一种通用方法，通过S-烷基化反应修饰手性中心诱导螺旋（CIH）肽的交联链。烷基化过程表现出高转化效率、选择性和底物耐受性。值得注意的是，尽管链上S-烷基化可能导致一对肽差向异构体，但主要的烷基化产物保留了其螺旋前体肽的螺旋结构。这种S-烷基化在还原条件下易于逆转，这为无痕修饰提供了一种简单方法。除了扩展CIH肽的化学空间外，该策略是首个已知能保留肽原始螺旋度的链上修饰平台。
