Synthesis and conformational study of two L-prolyl-L-leucyl-glycinamide analogues with a reduced peptide bond.
The peptide bond between Pro-Leu or Leu-Gly in Pro-Leu-Gly-NH2 was replaced by a CH2-NH function. The 1H and 13C n.m.r. studies demonstrated that HCl X Pro-Leu psi (CH2-NH)Gly-NH2 10 adopted a conformation in DMSO that is similar to the previously postulated beta-turn for the natural hormone. This was not the case for the other analogue. In vivo tests on 10 revealed an activity approximately equal to the natural compound and an increased toxicity.
D000818:Animals; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D004357:Drug Synergism; D007202:Indicators and Reagents; D007980:Levodopa / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship
D004151:Dipeptides; D007202:Indicators and Reagents; C050201:prolyl-leucyl-psi(methylamino)glycinamide; C050200:prolyl-psi(methylamino)leucyl-glycinamide; D007980:Levodopa; D010095:Oxotremorine; D009075:MSH Release-Inhibiting Hormone