Synthesis of cyclic peptides

US7589170B1 · kind B1 · utility

Assignee

• The University Of Queensland · AU

Inventors

• Mark Leslie Smythe · Forsayth, AU
• Wim Denis Frans Meutermans · Parnngurr, AU
• Gregory Thomas Bourne · Jindalee, AU
• Ross Peter McGeary · Brisbane, AU

Key dates

• Filing date: Sep 24, 1999
• Grant date: Sep 15, 2009
• Expiry date: Sep 24, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K7/64
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

This invention relates to methods for preparing cyclic peptides and peptidomimetic compounds in solution and bound to solid supports, and to cyclic peptide or peptidomimetic libraries for use in drug screening programs. In particular, the invention relates to a generic strategy for synthesis of cyclic peptides or peptidomimetics that enables the efficient synthesis under mild conditions of a wide variety of desired compounds. Two approaches were evaluated for their improvements in solution and solid phase synthesis of small cyclic peptides: positioning reversible N-amide substituents in the sequence; and applying native ligation chemistry in an intramolecular sense. Systematic investigation of the effects of preorganising peptides prior to cyclisation by using peptide cyclisation auxiliaries, and developing new linkers and peptide cyclisation auxiliaries to aid cyclic peptide synthesis gives surprising improvements in both yields and purity of products compared to the prior art methods. The combination of these technologies provides a powerful generic approach for the solution and solid phase synthesis of small cyclic peptides. The ring contraction and N-amide substitution technolo…