Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Methods Mol Biol. 2022;2371:101-115. doi: 10.1007/978-1-0716-1689-5_6.
Cyclic peptides are becoming increasingly important in drug discovery due to their specific binding properties, larger surface area compared to small molecules, and their ready and modular synthetic accessibility. In this protocol, we describe an on-resin, cleavage-inducing cyclization methodology for the synthesis of cyclic thiodepsipeptides and cyclic homodetic peptides using the 3-amino-4-(methylamino)benzoic acid (MeDbz) linker. We further describe three post-cyclization one-pot procedures, which include desulfurization, disulfide bond formation, and S-alkylation of cysteine residues.
环肽由于其特异性结合特性、与小分子相比更大的表面积以及易于制备和模块化的合成可及性，在药物发现中变得越来越重要。在本方案中，我们描述了一种在树脂上的、通过切割诱导环化的方法，用于使用 3-氨基-4-(甲氨基)苯甲酸（MeDbz）接头合成硫代二肽和同型二肽环肽。我们进一步描述了三种环化后的一锅法程序，包括脱硫、二硫键形成和半胱氨酸残基的 S-烷基化。
