Control of Biological Processes with Modified Nucleosides, Amino Acids, and Small-Molecule Probes

chemical biology;caged molecules;chemistry;bio-organic chemistry

Lusic, Hrvoje ; Paul Agris, Committee Member,Tatyana Smirnova, Committee Member,Jonathan Lindsey, Committee Member,Bruce Novak, Committee Member,Alex Deiters, Committee Chair,Lusic, Hrvoje ; Paul Agris ; Committee Member ; Tatyana Smirnova ; Committee Member ; Jonathan Lindsey ; Committee Member ; Bruce Novak ; Committee Member ; Alex Deiters ; Committee Chair

University:North Carolina State University

关键词: chemical biology;    caged molecules;    chemistry;    bio-organic chemistry;   

Others  :  https://repository.lib.ncsu.edu/bitstream/handle/1840.16/6214/etd.pdf?sequence=1&isAllowed=y

美国|英语

来源: null

【 摘 要 】

Several novel caging groups with a wide range of applications were designed. The caging groups were applied to the synthesis of molecular tools for control of gene expression. A number of RNA, DNA, and antisense-oligomer subunits were prepared. The caged nucleosides were site-specifically incorporated into corresponding oligonucleotide strands, using standard automated-synthesis protocols. The caged nucleosides were found to readily photolyse under biologically non-damaging UV-light (>365 nm). Spatio-temporal control over oligomers’ biological and/or catalytic activity was demonstrated with excellent on(or off) photo-triggered switches. Additionally, non-standard nucleosides 5-formylcytidine and N-[(9-D-ribofuranosyl-2-methylthiopurin-6-yl)carbamoyl]threonine were synthesized for incorporation into tRNA to elucidate the importance of the non-standard nucleoside modifications on codon recognition in RNA translation. Furthermore, tools for control over protein functions were designed. A set of novel unnatural amino acids were successfully synthesized and genetically (in vivo) incorporated into proteins using evolved orthogonal tRNA/synthetase pairs. Lastly, several caged protein kinase inhibitors were prepared, and used to study importance of kinase enzymatic activity in embryonic development of Xenopus laevis.