EXCEED THE SPACE PROVIDED. The long-term goal of this proposal is to better define relationships between structure and activity in aqueous solution. Specifically, the work proposed here will consider the facets of molecular structure relevant to affinity and specifity in aqueous association phenomonena. We will consider these issues in the context of small molecule chelates for various metal ions, in the development of high affinity protein-carbohydarte intereactions, and in the development of novel heterobivalent ligands for the matrix metalloprotease stromelysin. Our studies to define structure-function relationships in aqueous solution will facilitate the design and preparation of small molelcule ligands with a priori defined properties. These ligands could serve a wide variety of therapeutic roles, as agonist/antagonist ligands for various receptors and as inhibitors of various enzymes. PERFORMANCE SiTE(S) _anization, ci_,state) Department of Chemistry, Duke University, Durham, North Carolina KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Role on Project Eric Toone Department of Chemistry, Duke PI University PHS 398 (Rev. 05/01) Page _2 Form Page 2 Disclosure Permission StatemenE Applicable to SBIR/STTR Only. See instructions. [] Yes [] No ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057179-07
Application #
6839483
Study Section
Special Emphasis Panel (ZRG1-SSS-B (01))
Program Officer
Marino, Pamela
Project Start
1999-01-01
Project End
2006-12-31
Budget Start
2005-01-01
Budget End
2005-12-31
Support Year
7
Fiscal Year
2005
Total Cost
$308,000
Indirect Cost
Name
Duke University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Wilfong, Erin M; Du, Yu; Toone, Eric J (2012) An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1. Bioorg Med Chem Lett 22:6521-4
Wilfong, Erin M; Kogiso, Yuri; Muthukrishnan, Sivaramakrishnan et al. (2011) A multidisciplinary approach to probing enthalpy-entropy compensation and the interfacial mobility model. J Am Chem Soc 133:11515-23
Wilfong, Erin M; Locklear, Ursala; Toone, Eric J (2010) A single step purification for autolytic zinc proteinases. Bioorg Med Chem Lett 20:280-2
Snyder, Phillip W; Lee, Gwangrog; Marszalek, Piotr E et al. (2007) A stochastic, cantilever approach to the evaluation of solution phase thermodynamic quantities. Proc Natl Acad Sci U S A 104:2579-84
Debenham, Sheryl D; Snyder, Phillip W; Toone, Eric J (2003) Solid-phase synthesis for the identification of high-affinity bivalent lectin ligands. J Org Chem 68:5805-11
Lundquist, Joseph J; Toone, Eric J (2002) The cluster glycoside effect. Chem Rev 102:555-78
Griffiths, Jennifer S; Wymer, Nathan J; Njolito, Eugenia et al. (2002) Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase. Bioorg Med Chem 10:545-50
DiTusa, C A; Christensen, T; McCall, K A et al. (2001) Thermodynamics of metal ion binding. 1. Metal ion binding by wild-type carbonic anhydrase. Biochemistry 40:5338-44
DiTusa, C A; McCall, K A; Christensen, T et al. (2001) Thermodynamics of metal ion binding. 2. Metal ion binding by carbonic anhydrase variants. Biochemistry 40:5345-51
Lundquist, J J; Debenham, S D; Toone, E J (2000) Multivalency effects in protein--carbohydrate interaction: the binding of the Shiga-like toxin 1 binding subunit to multivalent C-linked glycopeptides. J Org Chem 65:8245-50