
Development of Streamlined Chemoenzymatic Glycan Remodeling Systems for Antibodies and Other Important GlycoproteinsAward last edited on: 5/22/2023
Sponsored Program
SBIRAwarding Agency
NIH : NIGMSTotal Award Amount
$1,788,600Award Phase
2Solicitation Topic Code
859Principal Investigator
Qiang YangCompany Information
Phase I
Contract Number: 1R43GM134816-01Start Date: 8/1/2019 Completed: 7/31/2021
Phase I year
2019Phase I Amount
$150,000Benefits:
1) stabilizing the enzyme for sustained activity, repeated use, and easy storage; 2) removing the protein purification steps for protein-GlcNAc acceptor and final products, thus greatly simplifying the process; 3) eliminating the potential problem of wild type enzyme contamination from the deglycosylation step. To achieve these objectives, we propose to pursue the following two specific aims in Phase I study. Aim 1 is to immobilize key enzymes for glycan remodeling of antibodies, which include: the endoglycosidase S2 (Endo-S2) from Streptococcus pyogenes, the Endo-S2 glycosynthase mutant (D184M), and an ?1,6-fucosidase for defucosylation. Different methods of immobilization will be investigated. Aim 2 is to develop reaction kits and simply protocols for streamlined application of the enzymatic glycan remodeling of antibodies. In prospective phase II research, the study will expand to other endoglycosidases, to cover other glycoproteins/glycopeptides, for both academic and industrial applications.
Public Health Relevance Statement:
Project Narrative This proposal research aims to develop efficient and streamlined cheomoenzymatic systems for glycan remodeling of antibodies and other important glycoproteins.
Project Terms:
Address; Adopted; Affect; Antibodies; Biological Process; Bos taurus structural-GP protein; Cell Adhesion; chemical synthesis; Chitosan; Complex; Coupling; crosslink; Development; Drug Kinetics; Endoglycosidases; Engineering; enzyme immobilization; Enzymes; Fucosidase; Glycopeptides; glycoprotein structure; Glycoproteins; glycosylation; Heterogeneity; Hybrids; Immobilization; Immobilized Enzymes; Immune response; immunogenicity; in vivo; Industrialization; International; Lactobacillus casei; Legal patent; Libraries; Magnetism; Maryland; Methods; mutant; new technology; novel; off-patent; particle; pathogen; Pathway interactions; Phase; phase 1 study; Polysaccharides; Post-Translational Protein Processing; Preparation; Procedures; Process; Property; prospective; Protein Glycosylation; protein purification; Proteins; Protocols documentation; Reaction; Research; Research Proposals; research study; scaffold; scale up; Sepharose; Site; Streptococcus pyogenes; Structure; success; System; technology development; Testing; Therapeutic; Transglutaminases; tumor progression; United States National Institutes of Health; Universities
Phase II
Contract Number: 5R43GM134816-02Start Date: 8/1/2019 Completed: 7/31/2021
Phase II year
2020(last award dollars: 2022)
Phase II Amount
$1,638,600Benefits:
1) stabilizing the enzyme for sustained activity, repeated use, and easy storage; 2) removing the protein purification steps for protein-GlcNAc acceptor and final products, thus greatly simplifying the process; 3) eliminating the potential problem of wild type enzyme contamination from the deglycosylation step. To achieve these objectives, we propose to pursue the following two specific aims in Phase I study. Aim 1 is to immobilize key enzymes for glycan remodeling of antibodies, which include: the endoglycosidase S2 (Endo-S2) from Streptococcus pyogenes, the Endo-S2 glycosynthase mutant (D184M), and an ?1,6-fucosidase for defucosylation. Different methods of immobilization will be investigated. Aim 2 is to develop reaction kits and simply protocols for streamlined application of the enzymatic glycan remodeling of antibodies. In prospective phase II research, the study will expand to other endoglycosidases, to cover other glycoproteins/glycopeptides, for both academic and industrial applications.
Public Health Relevance Statement:
Project Narrative This proposal research aims to develop efficient and streamlined cheomoenzymatic systems for glycan remodeling of antibodies and other important glycoproteins.
Project Terms:
Address; Adopted; Affect; Antibodies; Biological Process; Cell Adhesion; chemical synthesis; Chitosan; Complex; Coupling; crosslink; Development; Drug Kinetics; Endoglycosidases; Engineering; Enzymes; Fucosidase; Glycopeptides; glycoprotein structure; Glycoproteins; glycosylation; Heterogeneity; Hybrids; Immobilization; Immobilized Enzymes; Immune response; immunogenicity; in vivo; Industrialization; International; Lactobacillus casei; Legal patent; Libraries; Magnetism; Maryland; Methods; mutant; new technology; novel; particle; pathogen; Pathway interactions; Phase; phase 1 study; Polysaccharides; Post-Translational Protein Processing; Preparation; Procedures; Process; Property; prospective; Protein Glycosylation; protein purification; Proteins; Protocols documentation; Reaction; Research; Research Proposals; research study; scaffold; scale up; Sepharose; Site; Streptococcus pyogenes; Structure; success; System; technology development; Testing; Therapeutic; Transglutaminases; tumor progression; United States National Institutes of Health; Universities