Angiotensin II analogues with sulphur-containing side-chains in position 5- A structure-activity relationship study

Four sets of angiotensin TI (AngII) analogues with position 5 modifications , two agonist series with either Asp or Sar in position 1 and L-Phe in posi tion 8, and two antagonist series with again Asp or Sar in position 1 and L eu in position 8 were synthesized. Modifications in positions 5 were introd uced successively: Ile, Nle, Met, S-ethyl Cys, S-n-propyl-Cys, S-n-butyl Cy s S-t-butyl Cys and S-benzyl Cys in all four series. The study was undertak en in order to investigate the 5-position residue of AngII by replacing the hydrophobic side-chain by another containing an electrophilic moiety. The analogues were synthesised by solid phase synthesis using the Boc/Bzl or Fm oc/But strategy. Aii analogues were evaluated by their binding properties t o the ATI receptor on bovine adrenocortical membranes (bAT(1)). The results indicate that AngII analogues bind, irrespective of their agonistic or ant agonistic nature or of their position 1 modification, in a similar manner a nd that position 5 modifications without beta-branching behave in an additi ve manner towards their affinity.