Method for synthesis of proteins
AssigneeVanderbilt University
InventorJames P. Tam
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Abstract
A method for peptide synthesis is disclosed that requires neither protecting groups nor activation of the C-α carboxyl groups. The method comprises ligating a first molecule to a second molecule by promoting the orthogonal coupling of the molecules to each other. In an aspect of this method, an acyl-type reaction occurs between the molecules. The method contemplates the joining of molecules of variant size to each other, as well as the coupling of multiple identical molecules. The invention also covers the ligation of unprotected peptide, proteins or nonpeptide segments to prepare therapeutic products and synthetic vaccines with linear, circularized, or branched backbone structures, as well as the site-specific modification of peptides or proteins by lipidation and pegylation.
Claims13
A method of forming an amide bond between a first molecule and a second molecule, said first and second molecule independently selected from the group consisting of an amino acid, peptide, peptide mimetic, peptide scaffolding matrix and protein, said method comprising coupling said first molecule to said second molecule by means of an acyl rearrangement reaction through a five to seven membered ring intermediate without aid of a template, said coupling selected from the group consisting of
- (A) a thioesterification reaction comprising reacting a thiocarboxylic acid on either said first molecule or said second molecule with a 1,2-aminohaloethane moiety on either said second molecule or said first molecule, respectively;
- (B) a thioesterification reaction comprising reacting a thiocarboxylic acid on either said first molecule or said second molecule with a aziridine moiety on either said second molecule or said first molecule, respectively;
- (C) a disulfide exchange reaction comprising reacting an acyl mixed disulfide on either said first molecule or said second molecule with a 1,2-aminothiol moiety on either said second molecule or said first molecule, respectively;
- (D) a disulfide exchange reaction comprising reacting a thiocarboxylic moiety on either said first molecule or said second molecule with a 1,2-aminoethane moiety on either said second molecule or said first molecule, respectively;
- (E) an N-acylation reaction comprising reacting a 1,2-aminoethane imidazole moiety on either said first molecule or said second molecule with an acyl mixed disulfide moiety on either said second molecule or said first molecule, respectively;
- and
- (F) an O-acylation reaction comprising reacting a 1,2-aminoethane carboxylic moiety on either said first molecule or said second molecule with an acyl mixed disulfide moiety on either said second molecule or said first molecule, respectively.
A method of forming an amide bond between a first molecule and a second molecule, said first and second molecule independently selected from the group consisting of an amino acid, peptide, peptide mimetic, peptide scaffolding matrix, and protein, said method comprising coupling said first molecule to said second molecule by means of an acyl rearrangement reaction through a five to seven membered ring intermediate without aid of a template, said coupling performed by an aldehyde capture reaction comprising reacting a weak base moiety on either said first molecule or said second molecule with an aldehyde moiety on either said second molecule or said first molecule, respectively.
Dependencies are inferred from the claim text.