GOALI: Metal Complexes as Artificial Peptidases

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Dr. Nenad Kostic of Iowa State University is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry Program of the Chemistry Division and the MPS Office of Multidisciplinary Activities, under the Grant Opportunities for Academic Liaison with Industry (GOALI) program to produce new catalysts designed to cleave proteins at specific predetermined points along their molecular backbone. New metal complexes will be tested for their ability to split short artificial proteins, using the proteins' sulfur atoms to "anchor" the catalyst. Methods will be developed to suppress interference with efficient catalysis by aggregation of the catalyst and by reactions of the products. Specifically designed proteins (and artificially produced variants of native proteins) will be used to investigate the influence of several levels of protein structure on the efficiency of catalysis. The influence of folding of the protein on the rate of catalytic cleavage will be examined.The ability to split protein molecules at predetermined molecular locations will be important in biotechnology, and in developing further understanding of the functioning of complex biological systems. This program will produce new synthetic catalysts for important biochemical reactions. Discovery of such artificial enzymes will be useful in biotechnology and in the production of pharmaceuticals, as well as in experiments leading to control of the functioning of genetic information in developmental biology. Two pharmaceutical companies (BioNebraska and Merck) are collaborating in this research. Graduate students will be trained in state-of-the-art mass spectrometry techniques in industrial laboratories.