The syntheses of peptidylacridines; the synthesis of oligonucleotide acridine adducts; and solid state NMR studies of four benzamide neuroleptics

Chung Chow Chan, Purdue University

Abstract

This thesis describes two studies on 9-aminoacridines and one study on solid-state NMR of four representative benzamides. The objective of the first project is to determine the affinities of acridines with amino acid side chains of different chirality for DNA. The sc L- sc L- and sc D- sc D- enantiomers of phenylalanyl-N-9-acridinylphenylalaninamide were synthesized. The DNA-binding data of the sc L- sc L- enantiomer can be fitted to a Scatchard plot giving K and n values of (4.65 $\pm$ 2.71) $\times$ 10$\sp5$ and 0.30 $\pm$ 0.06, respectively. The binding data of the sc D- sc D- enantiomer could not be fitted to a Scatchard plot. The objective of the second project is to attach 9-aminoacridine to oligomers via a carboxyethylaminohexyl or carboxypropylaminohexyl linker arm. 9-(N-carboxyethyl)- and 9-(N-carboxypropyl)aminoacridines linked to 5$\sp\prime$-NH$\sb2$(CH$\sb2)\sb6$-OPO$\sb3$-TCAGTGGT-PO$\sb4$ were synthesized and purified by HPLC. These adducts will be tested for their ability to inhibit reverse transcription of the rabbit $\beta$-globin mRNA. The third project involves the solid-state NMR studies of four semi-rigid benzamide molecules; remoxipride (free base and the hydrochloride salt), FLA 797 and raclopride tartrate. The $\sp{13}$C-resonances of these molecules in the solution and solid-state were compared. The remoxipride free base and its hydrochloride salt showed good correlation whereas FLA 797 and raclopride tartrate showed significant differences between their solution and solid-state NMR spectra.

Degree

Ph.D.

Advisors

Byrn, Purdue University.

Subject Area

Pharmacology

COinS