Synthesis of fluorine-containing peptides. Analogues of angiotensin II containing hexafluorovaline.

Gamma, gammma, gammma, gammma', gamma', gammma'-Hexafluorovaline and derivatives have been prepared and incorporated into angiotensin II by fragment condensation and solid-phase peptide synthesis. Hexafluorovaline derivatives showed general resistance toward various enzymatic digestions and the tendency to racemize extensively upon carboxyl activation. When the angiotensin II analogues were assayed on rat uterus, [Hfv5]AII had 133% activity, [D-Hfv5]AII was inactive, and [Ac-Asn1,DL-Hfv8]AII was a potent inhibitor of angiotensin II in vitro and in vivo.