Cyclising peptides
AssigneeUniversity of Durham
InventorsSteven Cobb, Christopher Coxon, Graham Sandford
Life of this patent
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Abstract
A method for preparing a cyclic peptide, derivative or analogue thereof is described. The method comprises contacting a peptide, derivative or analogue thereof with a fluoro-heteroaromatic compound to cyclise the peptide, derivative or analogue thereof.
Claims18
A method for preparing a bridged peptide, derivative or analogue thereof, the method comprising contacting a reactant comprising a peptide, derivative or analogue thereof with a fluoro-heteroaromatic compound to form a bridged structure with the peptide, derivative or analogue thereof,
- wherein the fluoro-heteroaromatic compound comprises at least two halogen atoms, wherein all of the at least two halogen atoms are fluorine atoms or the at least two halogen atoms comprise at least one fluorine atom and at least one chlorine atom,
- the reactant comprises at least two nucleophilic side chains at least one of which comprises a thiol group, and the method is carried out with the reactant in solution using a solvent and the solvent is 2,2,2-trifluoroethanol (TFE), and
- the reactant is:
- a) a peptide;
- b) a peptide where one or more of the amino acids residues of the peptide are replaced by residues with similar side chains or peptide backbone properties;
- c) a peptide where terminal groups thereof are protected by N- and C- terminal protecting groups with similar properties to acetyl or amide groups;
- d) a peptoid;
- e) a retropeptoid;
- f) a peptide-peptoid hybrid;
- or
- g) a peptide where at least one of the amino acids residues of the peptide is a D-amino acid.
A method for producing a bridged peptide, derivative or analogue thereof in a “step-wise” fashion, the method comprising at least two steps sequentially, wherein the first step comprises contacting a reactant comprising a peptide, derivative or analogue thereof with a fluoro-heteroaromatic compound to create a chemically modified peptide, derivative or analogue thereof, and the second step comprises contacting the chemically modified peptide, derivative or analogue thereof with a fluoro-heteroaromatic compound to cyclise the chemically modified peptide, derivative or analogue thereof,
- wherein the fluoro-heteroaromatic compound comprises at least two halogen atoms, wherein all of the at least two halogen atoms are fluorine atoms or the at least two halogen atoms comprise at least one fluorine atom and at least one chlorine atom,
- the reactant comprises at least two nucleophilic side chains at least one of which comprises a thiol group, the solvent for the first step is 2,2,2-trifluoroethanol (TFE) and the solvent for the second step is dimethylformamide (DMF), and
- the reactant is:
- a) a peptide;
- b) a peptide where one or more of the amino acids residues of the peptide are replaced by residues with similar side chains or peptide backbone properties;
- c) a peptide where terminal groups thereof are protected by N- and C- terminal protecting groups with similar properties to acetyl or amide groups;
- d) a peptoid;
- e) a retropeptoid;
- f) a peptide-peptoid hybrid;
- or
- g) a peptide where at least one of the amino acids residues of the peptide is a D-amino acid.
Dependencies are inferred from the claim text.