New polypeptides and process for their manufacture

摘要

The invention comprises the tetradecapeptide H - Ser-Tyr-Ser-Met - Glu -(or GluNH2) - His-Phe - Arg - Try - Gly - Lys - Pro - Val - Gly-Lys - Lys - Arg - Arg - Pro - Val - Lys - Val-Tyr-ProOH or their derivatives wherein the free carboxylic acids are esterified with tertiary butyl alcohol, and free amino groups are blocked with tertiary butyloxycarbonyl (BOC) groups, physiologically tolerable acid addition salts or heavy metal complexes thereof and the preparation thereof by reacting BOC-Ser-Tyr-Ser-Met-Glu (OtBu)(- or GluNH2) - His - Phe - Arg-Try - Gly OH with H.Lys(BOC) - Pro - Val-Gly - Lys (BOC) - Lys(BOC) - Arg - Arg - Pro-Val - Lip (BOC) - Val - Tyr - ProOt (- Bu (Derivatives of the peptides also include alkyl esters, amides, hydrazides, N-acyl and N-protected compounds in addition to the above-mentioned. The tetra decapeptide used as starting material is prepared by stepwise condensation of amino acids or smaller peptide units through the following intermediates: Z-Arg(NO2)ProOCH3 (from Z-Arg(NO2)OH and HProOCH3, where Z is carbo benzoxy), H-Arg-(NO2)-ProOCH3, Z - Arg NO2 - ArgNO2 - ProOCH3, H - Arg (NO2) - Arg(NO2) - ProOCH3, T - Lys(BOC)-Lys(BOC) - Arg(NO2) - Arg (NO2) - ProOCH3 (where T is trityl), H Lys (BOC)-Lys (BOC)-Arg(NO2) - Arg(NO2) - Pro OCH3, PZ - Lys (BOC) - Pro - Val - Gly - Lys(BOC)Lys(BOC)-Arg(NO2)ARg(NO2) - ProOCH3 (where PZ is para - phenylazobenzyloxycarbonyl), the corresponding free acid and PZ-Lys (BOC)-Pro-Val - Gly - Lys(BOC) - Lys (BOC) - Arg - Arg-Pro - Val - Lys (BOC) - Val - Tyr - ProOtBu. PZ - Lys(BOC) - Pro - Val - Gly NHNH2 is prepared from the corresponding methyl ester and hydrazine. H-Val-Lys (BOC)-Val-Tyr-ProOtBu is prepared from its PZ-derivative through Z - Val - Tyr - Pro - OtBu (from Z - Val - TyrOH and HProOtBu) and H - Val-Tyr - Pro - OtBu. PZ - Val - Lys (BOC)OH is prepared from Pz-ValOH and H-Lys (BOC) OH. Specifications 872,332, 876,571, 857,892, 992,957 and 992,958 are referred to.