Research School of Chemistry, Australian National University, Canberra, ACT, 2601, Australia.
Chem Commun (Camb). 2022 Sep 27;58(77):10817-10820. doi: 10.1039/d2cc03510c.
Stapling of peptides renders them better drug candidates. We report a new peptide staple resembling the natural metabolite lanthionine ketenamine. The strategy is orthogonal to canonical amino acids, proceeds in water and allows for tailored linkers. We applied the approach to the identification of cyclic peptide inhibitiors of the Zika virus protease. The right linker length of the peptide staple proved crucial for maximising activity. The best stapled peptide showed one order of magnitude stronger enzyme inhibition than its linear analogue.
肽的订书钉使其成为更好的药物候选物。我们报告了一种类似于天然代谢产物硫醚酮的新型肽订书钉。该策略与典型氨基酸不同，在水中进行，并允许定制接头。我们将该方法应用于鉴定寨卡病毒蛋白酶的环状肽抑制剂。肽订书钉的正确接头长度对于最大限度地提高活性至关重要。最佳的订书钉肽显示出比其线性类似物强一个数量级的酶抑制作用。
