Carbohydrates play important and varied roles in the cell, and are of interest as targets for therapeutic intervention, clinical diagnosis, and as potential pharmaceuticals. While compounds capable of selectively serving as receptors (or ligands) have been designed for most biological molecules, very few have been described that are capable of high-affinity noncovalent binding to simple carbohydrates in aqueous solution. The P.I.'s laboratory has recently developed a series of compounds, based on highly substituted tercyclopentanes, that bind simple sugars and more complex liposaccharides in water with affinities two to three orders of magnitude tighter than any previously described synthetic receptors. The research described herein seeks to use these receptors, and analogous molecules, to develop a detailed understanding of the structural factors underlying carbohydrate binding. Through systematic variation of tercyclopentane carbohydrate receptors, the relative contributions of hydrogen bonding, conformational variability, stereochemistry, hydrophobic effects, CH-pi, and cation-pi interactions will be examined. NMR analyses of one of these compounds alone and complexed with carbohydrate guests will provide high-resolution structural information about the binding interactions. This research will provide insights vital to our understanding of fundamental glycobiology, to our ability to design carbohydrate-targeted pharmaceutical agents, and to the development of diagnostic devices (biosensors).

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM062825-01A2
Application #
6543183
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2002-08-01
Project End
2006-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$238,729
Indirect Cost
Name
University of Rochester
Department
Dermatology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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