This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Dale G. Drueckhammer at the SUNY Stony Brook whose research will further develop and demonstrate a general computer-based method for molecular design. The project is based on applications of the computer program CAVEAT, which is a unique program that allows the search of electronic databases for compounds having bonds that match a set of defined vectors. In continued development of this methodology, one focus will be on the incorporation of fluorescent groups into a glucose receptor designed using this approach to achieve fluorescence-based sensing. A new application of the method will be the design of novel peptide/protein receptors. These receptors will be based on the display of a pair of arsenic functionalities on a scaffold structure designed using CAVEAT such that they will form reversible covalent bonds with the thiol groups of a pair of specifically positioned cysteine residues in an alpha-helical peptide or protein. Another major application of this project will be the development of a novel nucleic acid mimic, designed to exhibit high affinity and selectivity in binding to a specific sequence of RNA. The design incorporates a sequence of purine and pyrimidine bases each attached to a furan moiety, with individual units connected via the furan rings by a linker structure identified using CAVEAT. This design will demonstrate a fundamental new concept into how to use CAVEAT-based design to display a regular repeating array of functionality on an oligomeric structure, an idea that is expected to have broader applications. The final proposed application is to explore a dimeric iron-ligand complex designed to perform controlled oxidation reactions with molecular oxygen as the sole oxidant. CAVEAT will be used to design a structure to link the pair of ligands to facilitate the splitting of molecular oxygen into a pair of reactive iron-oxygen species.
The broader impacts of this research will be to provide training to students in computer-based design methods and synthetic chemistry. In addition to PhD students, the project will provide training to undergraduates, and students in a combined BS/MS program. The design methods developed will be generally applicable to a wide variety of problems and applications in chemistry and related fields and may become a widely used approach to molecular design. The work has special relevance to sensor development, which may have applications in fields including medicine, the environment, defense, and homeland security. The improved virtual molecular databases that Professor Drueckhammer continues to develop, may bring their broad applicability to the attention of other investigators to whom they will be made readily available upon request.
