Synthesis of [1-(L- and [1-(D-2-hydroxy-3-mercaptopropanoic acid)-8-lysine]-vasopressin

Abstract

Analogues of [lysine]-vasopressin containing a hydroxy-group in place of the primary amino-group (both L- and D-configurations) were synthesized by coupling p-nitrophenyl N-[L-2-acetoxy-3-(benzylthio)propanoyl]-L-tyrosinate and O-benzyl-N-(D-3-benzylthio-2-hydroxypropanoyl)-L-tyrosine hydrazide with a crystalline heptapeptide. The pressor and uterotonic activities of the L-isostere were 431 and 17.9 i.u.mg^–1, respectively, and those of the D-diastereoisomer 0.913 and 0.015 i.u.mg^–1. The hormone analogues did not bind to neurophysin.