# Polymer Probes of Cell-Cell Interactions

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $301,559

## Abstract

Project Summary
 Cholera has a global burden of approximately 1.4 to 4.3 million cases per year with a 2-3% mortality rate.
Currently available vaccines provide limited protection with a ~65% efficacy rate over 5 years, and lower
protection rates in children under 5 years of age. Cholera toxin engages sugar ligands on epithelial cells as a
prelude to intoxication. About 11 % of American males between the ages of 15-44 are infertile or subfertile.
Half of male fertility cases are clinically idiopathic or unexplained, however, systematic review suggests that
over half of these cases are due to acrosomal failures. Engagement of sugar ligands by sperm receptor(s)
activates sperm acrosomal exocytosis in sperm, which is essential for fertilization of the egg to occur. In both
systems, the weak affinities of receptor and sugar ligand are converted into high avidity interactions through
multivalent engagement.
 Polymeric probes provide a versatile strategy to investigate and control these types of multivalent ligand-
receptor interactions. Polymerization chemistry lends itself to rapid assembly of repeating ligand units in a
single synthetic step. However, most polymerization strategies provide narrow limits on the spacing and
positioning of ligands that can be achieved. Thus, interpreting structure-activity relationships for polymers in
cellular systems is a challenge that hinders translation into therapeutic or diagnostic applications. Our
innovative approach is application of alternating copolymerization strategies developed in the Sampson
laboratory. Our recent discovery of the bicyclo[4.2.0]oct-1(8)-ene-8-carboxamide/cyclohexene system for ring-
opening metathesis allows the preparation of very long, alternating polymers with high monomer economy. The
chemistry lends itself to controlling sequence beyond alternation.
 Using our polymer chemistry, we will (1) define the spacing and accessibility requirements for in vitro and in
vivo inhibition of cholera intoxication; (2) identify the most physiologically relevant glyco-copolymer activators of
mouse sperm acrosomal exocytosis; and (3) screen sperm from fertile and subfertile human males for
glycopolymer-induced acrosomal exocytosis to define the structure-activity relationships that differentiate them.
The proposed polymers in combination with their structural and functional characterization provide entry to
possible therapeutics of cholera and diagnostics of male infertility and/or methods of male contraception.

## Key facts

- **NIH application ID:** 9853800
- **Project number:** 5R01GM097971-17
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** NICOLE S SAMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,559
- **Award type:** 5
- **Project period:** 2000-03-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853800

## Citation

> US National Institutes of Health, RePORTER application 9853800, Polymer Probes of Cell-Cell Interactions (5R01GM097971-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853800. Licensed CC0.

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