Studies on the inhibition of Moloney murine leukemia virus reverse transcriptase by N-tritylamino acids and N-tritylamino acid-nucleotide compounds.
N-Acylated derivatives of 8-(6-aminohexyl) amino-adenosine-5 '-phosphate were prepared and studied with regard to their effect on DNA synthesis by the Moloney leukemia virus reverse transcriptase. N-palmitoyl and N-nicotinyl derivatives and bis-8-(6-aminohexyl) amino-5'-AMP inhibited the enzyme partially using poly (rA).oligo d(pT)(16-18) as template-primer with [(3)H]dTTP. In order to increase hydrophobicity in the acyl component tethered to the 8-(6-aminohexyl) amino group on the adenine nucleotide, N-trityl-L-phenylalanine and the N-trityl derivatives of the o, m, and p-fluoro-DL-phenylalanine were initially examined for inhibition of the enzyme using the above template-primer system. The compounds all inhibited the reverse transcriptase with IC(50) values of approximately 60-80 microM. However, when N-trityl-m-fluoro-DL-phenylalanine was coupled to the nucleotide 8-(6-aminohexyl) amino-adenosine-5'-phosphate, the inhibitory activity of this compound increased significantly (IC(50) = 5 microM).
Hawtrey
Arthur
A
Division of Pharmacology, Department of Medicine, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Pieterse
Anton
A
van Zyl
Johann
J
Van der Bijl
Pieter
P
Van der Merwe
Marichen
M
Nel
William
W
Ariatti
Mario
M
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D000596:Amino Acids / Q000138:chemical synthesis / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D008979:Moloney murine leukemia virus / Q000201:enzymology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism*; D014320:Triphenylmethyl Compounds / Q000138:chemical synthesis / Q000378:metabolism*
D000596:Amino Acids; D018894:Reverse Transcriptase Inhibitors; D014320:Triphenylmethyl Compounds; D000249:Adenosine Monophosphate; C015667:8-(6-aminohexyl)amino-2'-AMP; D004247:DNA; D012194:RNA-Directed DNA Polymerase