Studies directed towards the development of cyclic peptide-based analogs of macrolide immunosuppressants

Abstract

A simple strategy for the facile synthesis of cyclic rapamycinpeptide hybrids is developed and the affinities of these synthetic hybrids for FKBP12 are evaluated. The results prompted to undertake a systematic study on the optimum length of the peptide cassette required for locking the binding domain of rapamycin in the specific conformation as present in its FKBP12-bound crystal structure. This led to the development of a high affinity FKBP12 ligand.