Site isolation and presentation of functionality are two key requirements for enzymatic catalysis. Researchers have developed synthetic systems that effectively mimic either the functionality or the isolation of enzyme active sites; creation of constructs that provide both of these attributes remains a significant challenge. We will use self-assembled monolayers (SAMs) on monolayer-protected gold clusters (MMPCs) to provide both the isolation and preorganization required to effectively replicate the behavior of flavoenzyme systems. There are three key thrusts to our proposed research: 1) The effective duplication of enzyme-cofactor interactions using the preorganization provided by the SAM, coupled with the control provided by the radial nature of the MMPC sidechains. 2) Fabrication of MMPC structures that provide effective isolation of cofactors buried within the SAM from solvent and other interfering species. 3) We will combine expertise gained from the above programs to design and fabricate fully functional mimics of the electron transferase family of flavoenzymes. These investigations will address key issues of recognition in water and control of enzyme mimic redox potentials, and will culminate with the creation of a functional electron shuttle designed to fully replicate the function of an electron transferase.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM059249-04
Application #
6431030
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Preusch, Peter C
Project Start
1999-04-01
Project End
2006-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$233,984
Indirect Cost
Name
University of Massachusetts Amherst
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
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