Glycopolymer Microarrays with Sub-Femtomolar Avidity for Glycan Binding Proteins Prepared by Grafted-To/Grafted-From Photopolymerizations

Daniel J Valles; Yerzhan S Zholdassov; Joanna Korpanty; Samiha Uddin; Yasir Naeem; David R Mootoo; Nathan C Gianneschi; Adam B Braunschweig

doi:10.1002/anie.202105729

Glycopolymer Microarrays with Sub-Femtomolar Avidity for Glycan Binding Proteins Prepared by Grafted-To/Grafted-From Photopolymerizations

Angew Chem Int Ed Engl. 2021 Sep 6;60(37):20350-20357. doi: 10.1002/anie.202105729. Epub 2021 Aug 11.

Authors

Daniel J Valles^{1

2

3}, Yerzhan S Zholdassov^{1

2

3}, Joanna Korpanty⁴, Samiha Uddin^{2

3}, Yasir Naeem^{2

3}, David R Mootoo^{1

3}, Nathan C Gianneschi^{4

5

6}, Adam B Braunschweig^{1

2

3

7}

Affiliations

¹ The PhD program in Chemistry, Graduate Center of the City University of New York, 365 5th Ave, New York, NY, 10016, USA.
² Advanced Science Research Center at the Graduate Center, The City University of New York, 85 St. Nicholas Terrace, New York, NY, 10031, USA.
³ Department of Chemistry, Hunter College, 695 Park Ave, New York, NY, 10065, USA.
⁴ Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA.
⁵ Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA.
⁶ Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA.
⁷ The PhD program in Biochemistry, Graduate Center of the City University of New York, 365 5th Ave, New York, NY, 10016, USA.

PMID: 34273126
DOI: 10.1002/anie.202105729

Abstract

We report a novel glycan array architecture that binds the mannose-specific glycan binding protein, concanavalin A (ConA), with sub-femtomolar avidity. A new radical photopolymerization developed specifically for this application combines the grafted-from thiol-(meth)acrylate polymerization with thiol-ene chemistry to graft glycans to the growing polymer brushes. The propagation of the brushes was studied by carrying out this grafted-to/grafted-from radical photopolymerization (GTGFRP) at >400 different conditions using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization on surfaces. The effect of brush height and the grafting density of mannosides on the binding of ConA to the brushes was studied systematically, and we found that multivalent and cooperative binding account for the unprecedented sensitivity of the GTGFRP brushes. This study further demonstrates the ease with which new chemistry can be tailored for an application as a result of the advantages of hypersurface photolithography.

Keywords: glycopolymers; lectins; lithography; microarrays; thiol-ene.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

Abstract

Publication types

Grants and funding