Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates.

Orthostatic cardiovascular reflexes were evaluated in conscious cynomolgus monkeys during interruption of the renin-angiotensin system with the renin inhibitor: RIP (Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys-OH). RIP was synthesized via solid phase techniques and purified to homogeneity. In vitro studies indicated that it exhibited classical competitive inhibition of renin with a KI of 2.

A conformationally constrained vasopressin analog with antidiuretic antagonistic activity.

Application of information derived from a three-dimensional model of vasopressin bound to its antidiuretic receptor resulted in the design and synthesis of a bicyclic vasopressin analog, [5,8-cyclo(1-beta-mercaptopropionic acid,2-phenylalanine,5-aspartic acid,8-lysine)]vasopressin. The analog acts as an antagonist of the antidiuretic activity of vasopressin.

Synthesis of [1, 6-cyclo (acetyl-1-L-glutamic acid, 2-D-phenylalanine, 3-D-tryptophan, 6-D-lysine)] luteinizing hormone-releasing hormone on poly-N-acrylylpyrrolidine resin.

The protected peptide, Ac-Glu(OBut)-D-Phe-D-Trp-Ser(But)-Tyr(But)-D-Lys (Z)-Leu-Arg(Tos)-Pro-Gly-NH2 was synthesized in a stepwise manner on a resin of poly-N-acrylylpyrrolidine using both acid cleavable N alpha-tert.-butyloxycarbonyl and base cleavable N alpha-fluorenylmethyloxycarbonyl protecting groups. After cleavage by ammonolysis in methanol, the tert.

Bidirectional synthesis of [5-aspartic acid] arginine vasopressin on poly-N-acrylylpyrrolidine resin.

In the proposed biologically active conformation of vasopressin at its antidiuretic receptor, the side-chain carboxamide moiety of the 5-position asparaginyl residue has been suggested to be an active element for the initiation of the antidiuretic response. [5-Aspartic acid] arginine vasopressin, the analog in which the -NH2 portion of the primary amide has been replaced by an -OH group, has been synthesized and tested for some of the pharmacological activities of vasopressin. The partially protected nonapeptide intermediate was assembled bidirectionally on a poly-N-acrylylpyrrolidine resin.

Limbless: a new genetic mutant in the chick.

A mutation in the chicken resulting in total amelia is described. Genetic analysis indicates that the limbless condition is due to an autosomal recessive gene. In the limbless embryos the apical ectodermal ridge is lacking.