A caged sperm-activating peptide that has a photocleavable protecting group on the backbone amide

A backbone-caged sperm-activating peptide (caged speract) that has a 2-nitrobenzyl group at a backbone amide and a vastly reduced affinity for its receptor (IC50 = 950 nM) was synthesized. UV irradiation of caged speract photocleaves the 2-nitrobenzyl group (tau(1/2)= 26 mus), restoring its affinity (IC50 = 0.67 nM) and ability to increase sperm intracellular pH and Ca2+, as intact speract. Backbone caging of the biological activity was more efficient than side chain caging, which adds a nitrobenzyl group on the peptide side chain. The backbone caging strategy described can be used as a general procedure to cage biologically active peptides, which have no side chain for introduction of a caging group. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.