STUDIES DIRECTED TOWARDS THE DEVELOPMENT OF CYCLIC PEPTIDE-BASED ANALOGS OF MACROLIDE IMMUNOSUPPRESSANTS

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