Native peptide cyclization, sequential chemoselective amidation in water
AssigneeThe Research Foundation for The State University of New York
InventorsQiang Zhang, Huan Chen
Life of this patent
Estimating the term…
Abstract
Disclosed herein are processes directed to Native Peptide Cyclization (NPC) and chemoselective methods enabling intramolecular and intermolecular peptidyl ligation without the need for premodification of starting peptides. NPC cyclizes unprotected linear peptides through controlled, sequential C- and N-terminal NPC simplifies peptide ligation, easing the labor-intensive nature of peptide synthesis, efficient cyclic peptide preparation and enabling cost-effective macrocycle-based therapeutics.
Claims21
A method of cyclizing peptides, said method comprising:
- i) reacting a at least one unprotected peptide containing a plurality of amino acids in an acidic aqueous solution, said peptide having a C-terminus end and an N-terminus end;
- ii) activating the C-terminus of at least one amino acid with an electrophilic activator in the solution;
- and iii) maintaining the solution at a temperature of about 0° C. to about 99° C. to form at least one stable amide bond that provides an N-to-S shift and at least one cyclized peptide.
12-26. (canceled)
A method of elongating peptides/proteins, said method comprising:
- i) reacting at least one unprotected first peptide containing a plurality of amino acids in an acidic aqueous solution having a pH of about 2 to about 5 at a temperature from about 0° C. to about 99° C., said first peptide having a C-terminus end and an N-terminus end and at least one thiol containing amino acid that is not the C-terminus or the N-terminus;
- ii) activating the C-terminus carboxylic acid of at least one amino acid of the first peptide with an electrophilic activator in the solution to provide thiolysis of the least one thiol containing amino acid to form at least one macro-thiolactone first peptide;
- iii) adding a at least one unprotected second peptides to the solution, said second peptide having a C-terminus end and an N-terminus end and at least one C-terminus containing a thiol group and at least one amino acid containing a thiol group that is not the C-terminus;
- and
- iv) increasing the pH of the acidic aqueous solution to about 6 to about 8 to provide for ligation of the at least one macro-thiolactone first peptide and at least one second peptide to form at least one elongated peptide.
Dependencies are inferred from the claim text.