Conjugation of Amine-Functionalized Polyesters With Dimethylcasein Using Microbial Transglutaminase

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Bioconjugation Chemistry

Background:

• Protein-polymer conjugates offer enhanced therapeutic properties like stability and reduced immunogenicity.
• Native proteins often face limitations in therapeutic applications due to short half-lives and immune responses.

Purpose of the Study:

• To enzymatically synthesize a water-soluble, biodegradable polymer.
• To functionalize the polymer with amine groups and hydrophilic chains for bioconjugation.
• To conjugate the modified polymer with a model protein using a mild enzymatic method.

Main Methods:

• Enzymatic synthesis of poly(glycerol adipate) (PGA(M)) using Candida antarctica lipase B.
• Acylation of PGA(M) with 6-(Fmoc-amino)hexanoic acid and poly(ethylene glycol) (mPEG12), followed by deprotection.
• Microbial transglutaminase-mediated conjugation of dimethylcasein with the modified polymer.
• Characterization using 1H NMR, FTIR, gel permeation chromatography, and SDS-PAGE.

Main Results:

• Successfully synthesized and characterized water-soluble PGA(M)-g-NH2-g-mPEG12.
• Demonstrated successful conjugation of dimethylcasein to the modified polymer.
• Characterization confirmed the structure and successful protein-polyester linkage.

Conclusions:

• Developed a novel, water-soluble polymer scaffold for protein modification.
• Established a mild enzymatic method for protein-polymer conjugation.
• The resulting conjugates hold potential for improved therapeutic protein delivery systems.