The syntheses of 9-benzylacridine and 9-phenylacridine analogs, and, The overproduction of mutant ribonuclease H and the synthesis of a ribonuclease H-octadeoxyribonucleotide bioconjugate as a potential anti-viral agent

Wu-Po Ma, Purdue University

Abstract

This thesis describes studies on oligodeoxyribonucleotide-acridine complex and RNase H-oligodeoxyribonucleotide conjugate. The objective of the first project is to synthesis benzylacridine and phenylacridine derivatives and then attach them to the 5$\sp\prime$-end of the octadeoxyribonucleotide, 5$\sp\prime$-TCAGTGGT-3$\sp\prime$, which is complementary to a sequence at about 100 bases from the 3$\sp\prime$-end of rabbit $\beta$-globin mRNA. The ability of these agents to inhibit the reverse transcription of the rabbit $\beta$-globin mRNA will be measured to assess the ability of these compounds to block important genes in the HIV virus. The objectives of the second project are to synthesize octadeoxyribonucleotide, 5$\sp\prime$-TCAGTGGT-3$\sp\prime$, with a cross coupling linker attached through the 5$\sp\prime$-end, to prepare wild type RNase H and mutant RNase H which retains a single cysteine residue, to conjugate the octadeoxyribonucleotide and mutant RNase H, and finally to determine the ability of such conjugate to cleave rabbit $\beta$-globin mRNA and a complementary octaribonucleotide in a sequence specific manner.

Degree

Ph.D.

Advisors

Davisson, Purdue University.

Subject Area

Biochemistry|Molecular biology|Organic chemistry

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