Effective peptides related to the luteinizing hormone releasing hormone from L-amino acids

US4721775A · kind A · utility

Assignee

• The Board of Regents of the University of Texas System · US

Inventors

• Karl Folkers · Austin, US
• Cyril Y. Bowers · New Orleans, US
• Pui-Fun L. Tang · Sha Tin, CN
• Minoru Kubota · Austin, US

Key dates

• Filing date: Aug 26, 1985
• Grant date: Jan 26, 1988
• Expiry date: Aug 26, 2005

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/13
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The chemical structure of the luteinizing hormone releasing hormone (LHRH) was elucidatd in 1971. Since then, a very large number of international investigators synthesized more than 100 monosubstituted and about 14 disubstituted analogs of LHRH. All of these analogs were synthesized from natural amino acids having the L-configuration. Not one of these approximately 114 analogs showed agonist activity equivalent to that of LHRH. Two of the 114 were about 60% as active, and neither one has had any utility. We have investigated the six individual L-amino acids which occur in positions 5, 7, and 8 of the four naturally occurring LHRH's which exist in porcine/ovine, salmon, and chicken tissue. There are a total of 16 peptides with these structural features, and we have discovered that not only one but five of these peptides are not only equivalent in certain assays in activity to LHRH, but that two of the five are surprisingly superior to LHRH in activity, and that two of the five have a unique and unpredictable dissociation of activity for the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). These five peptides are: PA0 A. p-Glu His Trp Ser His Gly Leu Arg P…