The goal of this project is to use novel combinatorial methods to isolate receptors for short (6-15 residue) peptides and epitopes in proteins. The receptors themselves will be peptides isolated from libraries made at the DNA level and searched by genetic means. Preliminary results have shown that these peptide-peptide complexes can exhibit extremely high selectivity and modest (micromolar range) affinity. Peptides pulled from libraries that bind other peptide target are potentially useful antibody substitutes if the affinity of binding can be increased or if the non-covalent interaction can be rendered irreversible. Two novel strategies are described to achieve this goal. One is to make use of chemical cross-linking methods that the PI has developed to covalently trap weak equilibria between the library derived peptide and its target. The second is to join the original peptide selected from the library via a linker to another peptide, which was selected to bind the original peptide/target complex. This so-called super-receptor concept should provide receptors that have extraordinary affinity and selectivity for the target epitope. Finally, these highly specific complexes between peptides of modest size are of intrinsic interest from a molecular recognition point of view. Therefore, some of these will be studied in detail using a variety of biophysical techniques, including multi-dimensional NMR. These studies will hopefully lead to a better understanding of how one would design peptide receptors de novo that are able to function in aqueous solution.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM060530-01A1
Application #
6266314
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Wehrle, Janna P
Project Start
2001-02-01
Project End
2004-01-31
Budget Start
2001-02-01
Budget End
2002-01-31
Support Year
1
Fiscal Year
2001
Total Cost
$247,738
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390