Enzyme inhibitors

Claim 1

A polypeptide analogue of the formula: ##STR38## where: Pro, Phe and His may be in substituted form; X=H, a lower aliphatic acyl (C 1 =C 5 ), t-butyloxycarbonyl, an aromatic acyl or an L- or D- amino- acyl residue, which may itself be N-protected similarly; Y=D- or L-His or other D- or L- basic or aromatic aminoacyl residue, or is absent; ##STR39## where the configuration at asymmetric centres * is either R or S, where in VIII the hydroxy group may be present as such or protected in either --OR 4 or ester ##STR40## form where R 4 is as given under W below and where R 1 and R 2 , the same or different= i Pro (isopropyl), i Bu (isobutyl), Bzl (benzyl) or other lipophilic or aromatic amino-acid side chain; R 3 =--H; lower alkyl (C 1 -C 5 ); or --SO 2 Ph, --SO 2 C 6 H 4 CH 3 (p), Boc, formyl or other N-protecting group; B=D- or L- Val or Ile or other D- or L- lipophilic aminoacyl residue; Z=D- or L- Tyr, Phe, His or other L- or D-aromatic amino-acyl residue; and W= (a) OH (b) --OR 4 where R 4 =(i) lower alkyl C 1 -C 5 (ii) cycloalkyl C 3 -C 7 or Bzl (c) --NH 2 (d) --NHR 5 or --N(R 5 ) 2 wherein R 5 is an N-protecting group or R 4 (e) L- or D-Lys (f) L- or D-Arg unprotected or as the ester or amide (g) L- or D-Ser and (h) amino alcohol derived from (e)-(g) unprotected protected as such or in ester or ether form; Z+W=alcohol derived from (i) L-Tyr (ii) L-Phe (iii) D-Tyr or D-Phe (iv) His such polypeptide being in the above form or modified by isosteric replacement of one or more remaining peptide bonds by reduced, --CH 2 --NH--, keto, ##STR41##hydroxy, --CH(OH)--CH 2 --, or hydrocarbon, --CH 2 --CH 2 -- isosteric links and further being in free form or in protected form at one or more remaining peptide, carboxyl, amino, hydroxy or other reactive groups.