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 (tau1/2=26 micros), 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.
Tatsu
Yoshiro
Y
National Institute of Advanced Industrial Science and Technology, Midorigaoka, 563-8577, Ikeda, Japan.
Nishigaki
Takuya
T
Darszon
Alberto
A
Yumoto
Noboru
N
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000528:radiation effects*; D010782:Photolysis; D015202:Protein Engineering; D012617:Sea Urchins; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D005456:Fluorescent Dyes; D009842:Oligopeptides; D010455:Peptides; C028364:speract; D002118:Calcium