Synthesis and biological activity of novel backbone-bicyclic substance-P analogs containing lactam and disulfide bridges.

ABSTRACT

A biased library of 60 novel backbone-bicyclic Substance P analogs was prepared by the simultaneous multiple peptide synthesis method. The peptides, containing both a lactam and a disulfide ring, were synthesized by combined Boc and Fmoc chemistries, and were cyclized on the resin. Cleavage of the S-benzyl group and oxidation of the sulfhydryl groups was enabled by adaptation of the diphenylsulfoxidetrichloromethylsilane method to solid-phase synthesis. The peptides were screened for NK-1 and NK-3 activity, and were found to be weak agonists.