Invention Grant
- Patent Title: Auxiliary for amide bond formation
- Patent Title (中): 辅助酰胺键形成
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Application No.: US09787840Application Date: 1999-09-24
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Publication No.: US07718598B1Publication Date: 2010-05-18
- Inventor: Mark Leslie Smythe , Wim Denis Frans Meutermans
- Applicant: Mark Leslie Smythe , Wim Denis Frans Meutermans
- Applicant Address: AU Brisbane, Queensland
- Assignee: The University of Queensland
- Current Assignee: The University of Queensland
- Current Assignee Address: AU Brisbane, Queensland
- Agency: Haynes and Boone, LLP
- Priority: AUPP6165 19980925
- International Application: PCT/AU99/00812 WO 19990924
- International Announcement: WO00/18789 WO 20000406
- Main IPC: C07K7/00
- IPC: C07K7/00 ; C07K14/00

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 programmes. 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 preorganizing 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 technology of the invention provide improved methods for the synthesis of cyclic peptides and peptidomimetics. When used in conjunction with linker strategies, this combination provides solid-phase avenues to cyclic peptides and peptidomimetics.
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