Amide based glucagon and superfamily peptide prodrugs

摘要

Prodrug formulations of glucagon superfamily peptides are provided wherein the glucagon superfamily peptide has been modified by the linkage of a dipeptide to the glucagon superfamily through an amide bond linkage. The prodrugs disclosed herein have extended half lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

主权项

1. A complex comprising the structure:
 A-B-Q; wherein Q is a glucagon superfamily peptide; A is an alpha-amino acid or an alpha-hydroxy acid, wherein when the alpha-carbon is chiral, A is in the D-stereochemical configuration; B is an N-alkylated amino acid linked to Q through an amide bond between A-B and a primary amine of Q; wherein A, B, or the amino acid of Q to which A-B is linked is a non-coded amino acid, further wherein the chemical cleavage half-life (t1/2) of A-B from Q is at least about 1 hour to about 1 week in PBS under physiological conditions.