Systematic Evaluation of Macromolecular Carbohydrate-LectinRecognition Using Precision Glycopolymers
Authors:
Cole A. Williams*, Daniel J. Stone*, Soumil Y. Joshi, Gokhan Yilmaz, Parisa Farzeen, Sungjin Jeon, Zamira Harris-Ryden, C. Remzi Becer, Sanket A. Deshmukh and Cassandra E. Callmann
Affiliation:
Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States
Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
Description:
The precise modulation of protein-carbohydrate interactions is critical in glycobiology, where multivalent bindinggoverns key cellular processes. As such, synthetic glycopolymers are useful for probing these interactions. Herein, we developedprecision glycopolymers (PGPs) with unambiguous local chemical composition and well-defined global structure and systematicallyevaluated the effect of polymer length, hydrophobicity, and backbone hybridization as well as glycan density and identity on thebinding to both mammalian and plant lectins. Our studies identified glycan density as a critical factor, with PGPs below 50% graftingdensity showing significantly weaker lectin interactions. Coarse-grained molecular dynamics simulations suggest that the observedphenomena may be due to a decrease in carbohydrate-carbohydrate interactions in fully grafted PGPs, leading to improved solventaccessibility. In functional assays, these PGPs reduced the cell viability and migration in 4T1 breast cancer cells. Our findingsestablish a structure−activity relationship in glycopolymers, providing new strategies for designing synthetic glycomacromoleculesfor a myriad of applications.
Publications:
- Cole A. Williams, Daniel J. Stone, Soumil Y. Joshi, Gokhan Yilmaz, Parisa Farzeen, Sungjin Jeon, Zamira Harris-Ryden, C. Remzi Becer, Sanket A. Deshmukh and Cassandra E. Callmann; Systematic Evaluation of Macromolecular Carbohydrate-Lectin Recognition Using Precision Glycopolymers; Biomacromolecules, 2024
Tags:
Bottlebrush polymers Carbohydrates Chemical biology Coarse-grained simulation PolymersRelated Projects:
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