Pseudo native chemical ligation
AssigneeGryphon Therapeutics, Inc.
InventorsChristie L. Hunter, Paolo Botti, James A. Bradburne, Shiah-yun Chen, Sonya Cressman, Stephen B. H. Kent, Gerd G. Kochendoerfer, Donald W. Low
Life of this patent
Estimating the term…
Abstract
The present invention concerns methods and compositions for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond (see FIG. 1). The invention further provides methods and uses for such proteins and derivatized proteins. The invention is particularly suitable for use in the synthesis of optionally polymer-modified, synthetic bioactive proteins, and of pharmaceutical compositions that contain such proteins.
Claims5
A method for synthesizing a desired polypeptide of formula:
- aaNH2-Q-aax-aay-W-aaCOOH
- wherein Q and W each denote the optional presence of one or more additional amino acid residues, aaNH2 denotes the N-terminal amino acid residue of the polypeptide;
- aax and aay denote internal adjacent amino acid residues, having side chains x and y, respectively, and wherein aay is a non-ribosomally synthesized amino acid residue and aaCOOH denotes the C-terminal amino acid residue of the polypeptide;
- said method comprising:
- (A) ligating a first peptide having the formula:
- aaNH2-Q-aax-COSR, wherein R is any group compatible with the thioester group, to a second peptide having the formula:
- Cys-W-aaCOOH to thereby form the polypeptide:
- aaNH2-Q-aax-Cys-W-aaCOOH;
- and
- (B) incubating said polypeptide in the presence of a reagent Raa-X, where Raa is a group whose structure comprises the side chain of amino acid residue aay;
- and X is a good leaving group;
- said incubation being under conditions sufficient to form said desired polypeptide.
Dependencies are inferred from the claim text.