First Advisor

John J. Perona

Date of Award


Document Type


Degree Name

Bachelor of Science (B.S.) in Biology and University Honors




Drugs -- Design, Aminoacyl-tRNA synthetases -- Synthesis




Substrate analogs are small molecules that aid in the understanding of enzyme structure-­‐function relationships. By careful design they can be utilized to probe the nature of the transition state in catalysis, and to assist in the process of rational drug design. Aminoacyl-­‐sulfamoyl adenylate transition state analogs (aa-­‐ AMS) are analogs of the aminoacyl adenylate reaction intermediate in aminoacylation by aminoacyl-­‐tRNA synthetases (aaRS). To better understand the chemical mechanism of aaRS, aa-­‐AMS are used in crystallography experiments where x-­‐ray diffraction helps reveal interactions crucial to catalysis. Here we report the complete synthesis and purification of Ile-­‐AMS. The four-­‐step process proceeds via a sulfamoyl-­‐adenylate precursor, from which a library of aa-­‐AMS can then be generated by the addition of particular amino acids. After addition of the amino acid 5 the product is put through an acid work up and purification step, giving an 85% experimental yield. Because commercially produced aa-­‐AMS are no longer available, assembly of a library of aa-­‐AMS would be beneficial for future research both at PSU and through collaboration with other research teams worldwide.


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An undergraduate honors thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Science In University Honors and Microbiology/ Molecular Biology.

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