Biofunctional evaluation of two hydrogen bonds stabilizing the beta-turn in the acyclic component of oxytocin.
The depsipeptide [8-alpha-hydroxyisocaproic acid, 9-glycolic amide]-oxytocin, which has ester linkages replacing the peptide linkages between the 7th and 8th and the 8th and 9th residues of oxytocin, has been synthesized by a (6 + 3) condensation of Boc-tocinoic acid with Pro-O-HyIc-O-Glyc-NH2, followed by deprotection of the resulting product. The analog exhibited the following activities in rats: 258 +/- 11 and 28 +/- 5 U/mg, uterus in vitro in the absence and presence, respectively, of Mg+2; 54 +/- 4 U/mg, uterus in vivo; 19.3 +/- 2.1 U/mg, milk ejection; 0.153 +/- 0.026 U/mg, antidiuretic activity; and no pressor activity. The need for the presence of the peptide linkages mentioned above as sources for internal hydrogen bonds to stabilize the "biologically significant" conformation is discussed.
D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D004231:Diuresis / Q000187:drug effects*; D004355:Drug Stability; D005260:Female; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008893:Milk Ejection / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011247:Pregnancy; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D014590:Uterine Contraction / Q000187:drug effects
D007202:Indicators and Reagents; D010121:Oxytocin