Synthesis of peptides by fragment condensation on a solid support. II. A scheme for preparation of 4,8-disubstituted vasopressins evaluated on 8-arginine-vasopressin.
A convenient scheme for the synthesis of 4,8-disubstituted vasopressins has been designed and its usefulness evaluated in the preparation of one of the parent hormones, 8-arginine-vasopressin. The main feature of the scheme involves preparation of two protected tripeptide fragments, Z-Cys(Bzl)-Tyr(Bzl)-Phe and Boc-Asn(Mbh)-Cys(Bzl)-Pro which are incorporated in a synthesis on a solid support. Both tripeptides were prepared conventionally with the carboxyl groups protected as benzyl esters. The benzyl-ester groups were removed by transesterification with 2-dimethylaminoethanol and subsequent hydrolysis. To avoid racemization in the coupling step with the fragment containing a C-terminal phenylalanine, N-hydroxysuccinimide was added. After removal of the peptide from the resin, deprotection, oxidation and desalting, final purification was effected by ion-exchange chromatography. Apart from the main product, which exhibited full pressor activity, only small amounts of impurities could be isolated.
D001127:Arginine Vasopressin / Q000032:analysis / Q000138:chemical synthesis*; D001216:Asparagine; D003545:Cysteine; D010446:Peptide Fragments; D010455:Peptides / Q000032:analysis / Q000138:chemical synthesis*; D010649:Phenylalanine; D011392:Proline; D014443:Tyrosine; D014667:Vasopressins / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D010446:Peptide Fragments; D010455:Peptides; D014667:Vasopressins; D001127:Arginine Vasopressin; D014443:Tyrosine; D010649:Phenylalanine; D001216:Asparagine; D011392:Proline; D003545:Cysteine