A comprehensive study on the effect of backbone stereochemistry of a cyclic hexapeptide on membrane permeability and microsomal stability

Backbone stereochemistry of cyclic peptides has been reported to have a great influence on microsomal stability and membrane permeability, two important factors that determine oral bioavailability. Here, we comprehensively investigated the correlation between the backbone stereochemistry of cyclic hexapeptide stereoisomers and their stability in liver microsomes, as well as passive membrane permeability. The effect of backbone stereochemistry of a cyclic hexapeptide on membrane permeability and metabolic stability was comprehensively evaluated. Besides, the effect of side chain structures on the pharmacokinetic properties was investigated.