First Advisor
John J. Perona
Date of Award
5-23-2013
Document Type
Thesis
Degree Name
Bachelor of Science (B.S.) in Biology and University Honors
Department
Biology
Subjects
Drugs -- Design, Aminoacyl-tRNA synthetases -- Synthesis
DOI
10.15760/honors.28
Abstract
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.
Rights
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Persistent Identifier
http://archives.pdx.edu/ds/psu/10242
Recommended Citation
Nilsson, Emil Mikael, "Synthesis of Sulfamoyl‐Aminoacyl Adenylate Analogs for use in Protein‐RNA Structure Determination" (2013). University Honors Theses. Paper 25.
https://doi.org/10.15760/honors.28
Comments
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.