METHODS FOR COUPLING TARGETING PEPTIDES ONTO RECOMBINANT LYSOSOMAL ENZYMES FOR IMPROVED TREATMENTS OF LYSOSOMAL STORAGE DISEASES

摘要

Described herein are methods of making targeting peptides conjugated to recombinant lysosomal enzymes by modifying the amino (N)-terminus and one or more lysine residues on recombinant human lysosomal enzymes using a first crosslinking agent to give rise to first crosslinking agent modified recombinant human lysosomal enzymes, modifying the first amino acid within a short linker at the amino (N)-terminus on a variant IGF-2 peptide using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short linker. Also described herein are conjugates synthesized characterized as having higher affinities for the IGF2/CI-MPR receptor and cellular uptake using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.