Synthesis and biological evaluation of oxytocin analogues containing L-alpha-t-butylglycine [Gly(Bu t)] in positions 8 or 9.
We report the solid phase synthesis and some pharmacological properties of seventeen new oxytocin (OT) analogues. Basic modification at positions 8 and/or 9 (introduction of L-alpha-t-butylglycine [Gly(Bu(t))]) was combined with D-Cys(6), D-Tyr(Et)(2), Mpa(1) or Pen(1) modifications and their various combinations. We also present properties of two previously reported re-synthesized analogues ([Gly(Bu(t))(8)]OT and [Mpa(1), Gly(Bu(t))(8)]OT). The analogues were tested for rat uterotonic activity in vitro, in the rat pressor assay and for binding affinity to human OTR.
Fragiadaki
Maria
M
Department of Pharmacy, Laboratory of Pharmacognosy and Chemistry of Natural Products, University of Patras, GR-26500 Patras, Greece.
Magafa
Vassiliki
V
Slaninová
Jirina
J
Cordopatis
Paul
P
D000818:Animals; D002460:Cell Line; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D010121:Oxytocin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D010121:Oxytocin; D005998:Glycine