Cell-cell interactions are fundamental to the survival of a multi-cellular organism. Control and diagnosis of normal and abnormal cell-cell interactions is important in all areas of human health ranging from embryonic development and immune function to uncontrolled tumor growth in cancer and infectious disease. Our long-term goal is the development of defined polymer systems that can be used for activation, inhibition, and discovery of cell-surface receptors to unravel these complex cell-cell interactions. Our objectives in this proposal are 1) to develop mimics of the zona pellucida moieties that initiate the sperm acrosome reaction and which may be used to identify the sperm zona pellucida receptors;2) to develop methods to identify extracellular receptors that are in low abundance;and 3) to develop alternating polymer structures that will advance our understanding of biology. Our hypothesis is that control of functional group spacing, backbone flexibility, and functional group variability in polymer synthesis will provide a powerful, molecular approach to elucidate cell-cell interactions. We expect to establish the appropriate mixture and density of sugars for optimally activating the sperm acrosome reaction and to develop a general method for isolating and identifying components of membrane-bound receptor complexes. Further development of alternating ring-opening metathesis polymerization chemistry will provide long, linear polymers for displaying alternating functional groups and will enable application of the methods developed in this work to the study of cell-cell interaction in a wide variety of biological systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
9R01GM097971-10
Application #
8108215
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2000-03-01
Project End
2015-08-31
Budget Start
2011-09-20
Budget End
2012-08-31
Support Year
10
Fiscal Year
2011
Total Cost
$284,193
Indirect Cost
Name
State University New York Stony Brook
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Huang, He; Rodolis, Maria T; Bhatia, Surita R et al. (2017) Sugars Require Rigid Multivalent Displays for Activation of Mouse Sperm Acrosomal Exocytosis. Biochemistry 56:2779-2786
Rodolis, Maria T; Huang, He; Sampson, Nicole S (2016) Glycopolymer induction of mouse sperm acrosomal exocytosis shows highly cooperative self-antagonism. Biochem Biophys Res Commun 474:435-440
Parker, Kathlyn A; Sampson, Nicole S (2016) Precision Synthesis of Alternating Copolymers via Ring-Opening Polymerization of 1-Substituted Cyclobutenes. Acc Chem Res 49:408-17
Lee, Siyeon; Wang, Wei; Lee, Younjoo et al. (2015) Cyclic acetals as cleavable linkers for affinity capture. Org Biomol Chem 13:8445-52
Tan, Li; Li, Guofang; Parker, Kathlyn A et al. (2015) Ru-Catalyzed Isomerization Provides Access to Alternating Copolymers via Ring-Opening Metathesis Polymerization. Macromolecules 48:4793-4800
Wu, Linghui; Sampson, Nicole S (2014) Fucose, mannose, and ?-N-acetylglucosamine glycopolymers initiate the mouse sperm acrosome reaction through convergent signaling pathways. ACS Chem Biol 9:468-75
Tan, Li; Parker, Kathlyn A; Sampson, Nicole S (2014) A Bicyclo[4.2.0]octene-Derived Monomer Provides Completely Linear Alternating Copolymers via Alternating Ring-Opening Metathesis Polymerization (AROMP). Macromolecules 47:6572-6579
Romulus, Joy; Tan, Li; Weck, Marcus et al. (2013) Alternating ROMP copolymers containing charge-transfer units. ACS Macro Lett 2:749-752
Song, Airong; Walker, Stephen G; Parker, Kathlyn A et al. (2011) Antibacterial studies of cationic polymers with alternating, random, and uniform backbones. ACS Chem Biol 6:590-9
Song, Airong; Parker, Kathlyn A; Sampson, Nicole S (2010) Cyclic alternating ring-opening metathesis polymerization (CAROMP). Rapid access to functionalized cyclic polymers. Org Lett 12:3729-31

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