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

摘要

Modification of the amino (N) -terminal and one or more lysine residues on the recombinant human lysosomal enzyme using a first cross-linking agent to produce a first cross-linker-modified recombinant human lysosomal enzyme, and using a second cross-linker to produce a variant IGF-2 peptide Modified mutant IGF-2 peptide is generated by modifying the first amino acid in the short linker at the amino (N) -terminal to generate a second cross-linker-modified variant IGF-2 peptide and then a second cross-linker-modified variant IGF- A method for producing a targeted peptide conjugated to a recombinant lysosomal enzyme by conjugating a modified recombinant human lysosomal enzyme is described herein. Conjugates characterized by having higher affinity and higher cell uptake for the IGF2 / CI-MPR receptor synthesized using the methods disclosed herein are also described herein. Methods of treatment using the disclosed conjugates are also described herein.