Purification of enkephalin, an endogenous composition in the human body and synthesis of same

US4105651A · kind A · utility

Assignee

• The United States of America as represented by the Department of Health, Education and Welfare · US

Inventor

• John Hughes · Coon Rapids, US

Key dates

• Filing date: Mar 15, 1976
• Grant date: Aug 8, 1978
• Expiry date: Mar 15, 1996

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The purification of an endogenous composition isolated from mammalian brain tissue and termed enkephalin ("in the head"). Enkephalin is recovered from brain tissue by acetone solution and purified by means of column and thin layer chromatography. The composition which is a mixture of two pentapeptides, namely, (a) H-Tyr-Gly-Gly-Phe-Met-OH and (b) H-Tyr-Gly-Gly-Phe-Leu-OH wherein the ratio of a:b is from 3:1 to 4:1 has been found to be a non-addictive narcotic and an opiate agonist. The synthesis of the pentapeptide composition from the known structure above is accomplished by conventional solution techniques of protection of the amino groups, such as t-butyloxycarbonyl, benzyloxycarbonyl, and t-amyloxycarbonyl, or the solid phase peptide synthesis of R. Bruce Merrifield using a polymeric support and the same or similar amine protecting groups.