Collect. Czech. Chem. Commun. 1988, 53, 2604-2616

Synthesis and properties of analogues of vasopressin with 1-aminocyclopropane-1-carboxylic acid in position 9

Zdenko Procházkaa, Juris E. Ancansa, Jiřina Slaninováa, Alena Machováb, Tomislav Bartha, Jana Škopkováa, Miloš Buděšínskýa, Františka Pavlíkovác and Michal Lebla

a Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6
b Research Institute for Pharmacy and Biochemistry, 194 09 Prague 9
c Prague Institute of Chemical Technology, 166 28 Prague 6


Solid phase methodology on benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with non-coded amino acid, 1-aminocyclopropane 1-carboxylic acid, in position 9. Two analogues of lysine-vasopressin ([Lys8, Acc9]vasopressin (I) and Gly3-[Lys8, Acc9]vasopressin (II)) and one analogue of arginine-vasopressin ([Arg8, Acc9]vasopressin (III)) have been synthesized. The dubious value of the biological activity of [Lys8, D-Ala9]vasopressin was reevaluated and [Lys8, L-Ala9]vasopressin was also synthesized and tested for the comparison. Differences in solution conformation of these two analogues were studied by 1H and 13C NMR spectroscopy. Biological activities of all analogues were either significantly lowered or almost completely eliminated. Analogues I-III were found to be completely inactive in analgesia and the CNS activities tested (active and passive avoidance).