SYNTHESIS AND BIOLOGICAL-ACTIVITY OF NOVEL BACKBONE-BICYCLIC SUBSTANCE-P ANALOGS CONTAINING LACTAM AND DISULFIDE BRIDGES

A biased library of 60 novel backbone-bicyclic Substance P analogs was prepared by the simultaneous multiple peptide synthesis method. The p eptides, containing both a lactam and a disulfide ring, were synthesiz ed by combined Boc and Fmoc chemistries, and were cyclized on the resi n. Cleavage of the S-benzyl group and oxidation of the sulfhydryl grou ps was enabled by adaptation of the diphenylsulfoxide-trichloromethyls ilane method to solid-phase synthesis. The peptides were screened for NK-1 and NK-3 activity, and were found to be weak agonists. (C) Munksg aard 1997.