Poly(β-Gal-Thr): A New Scalable Synthetic Mucin

Author

Manuel A. Lema, CUNY City CollegeFollow

Date of Award

2022

Document Type

Thesis

Department

Chemistry

First Advisor

Barbara Zajc

Keywords

Mucin, Mucus, Snail, Galactose, Threonine, Polymer

Abstract

A method for the preparation of glycosylated polypeptides via the nucleophilic ring-opening polymerization of a glycosylated N-carboxyanhydride (NCA) monomer is reported. The synthesis of 2,3,4,6-tetraacetyl-β-galactose-threonine N-carboxyanhydride (β-AcO-Gal-Thr-NCA) monomer in 5 steps with an 8 % overall yield is described, and the single-crystal X-ray structure is provided. The effect of a series of Ni⁰-based organometallic initiators, nucleophilic amine initiators, co-catalysts, and solvents on the polymerization were explored. The kinetics of the three most promising conditions were studied in greater detail. The conditions that provided the highest yield, low polydispersity (Ð), and excellent control over degree of polymerization ( ), while being amenable to gram-scale reactions, involved the nucleophilic initiator lithium hexamethyldisilazide (LiHMDS) and the cocatalyst 1,3-bis(2-hydroxyhexafluoroisopropyl) benzene (HFAB) in the nonpolar solvent CH₂Cl₂. A detailed analysis of this polymerization revealed that two propagation reactions proceed simultaneously, although at substantially different rates. These optimized polymerization conditions provide a route towards the synthesis of polymers that mimic the structures and properties of the highly glycosylated PTS domains of secreted mucin proteins.

Recommended Citation

Lema, Manuel A., "Poly(β-Gal-Thr): A New Scalable Synthetic Mucin" (2022). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/1001