Chemical synthesis and biological activity of peptides incorporating an ether bridge as a surrogate for a disulfide bond
Rui Zhao, Pan Shi, Junyou Chen, S. S. Sun, Jingnan Chen, Jibin Cui, Fangming Wu, Ge‐Min Fang, Changlin Tian, Jing Shi, Donald Bierer, Lei Liu, Yi‐Ming Li
Abstract
, using an ether-containing diaminodiacid as the key building block, obtained by the stereoselective ring-opening addition reaction of an aziridine skeleton with a hydroxy group. NMR studies indicated that the derivatives with an ether surrogate bridge exhibited very small change of their three-dimensional structures. The analogs obtained using this novel substitution strategy were found to be more stable than the original peptide in oxidative and reductive conditions; without a loss of bioactivity. This strategy is therefore proposed as a practical and versatile solution to the stability problems associated with cysteine-rich peptides.