Synthesis of N-substituted peptide amides

US4569967A · kind A · utility

Assignee

• Salk Institute for Biological Studies · US

Inventors

• Wayne D. Kornreich · San Diego, US
• Harry A. Anderson · San Diego, US
• John S. Porter · Leucadia, US
• Jean E. F. Rivier · Village of La Jolla, US

Key dates

• Filing date: Oct 24, 1983
• Grant date: Feb 11, 1986
• Expiry date: Oct 24, 2003

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K1/04
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Peptide N-alkylamides, and other C-terminal N-substituted amides, can be synthesized using solid-phase synthesis on a benzene-containing resin which is suitably methylated. Reactive amino groups are attached directly or indirectly to the methyl groups, for example, such as by reacting commercially available chloromethylated polystyrene resins with an alkylamine to create a resin-amine. The C-terminal amino acid of the desired peptide is linked to the resin-amine via an amide linkage, and the peptide is thereafter built in normal fashion. Treatment of the completed peptide intermediate with HF is effective to both effect deprotection and cleave the peptide from the resin in the form of the N-substituted amide. Examples include peptide N-ethylamides, N-fluoroethylamide, N-anilides and other substituted N-benzylamides.