Antiviral nucleotide drug delivery via amino acid phosphoramidates

Carston R. Wagner, Edward J. McIntee, Shu Ling Chang, Cheryl Zimmerman

Research output: Contribution to journalArticle

Abstract

Our laboratory has developed a strategy for the delivery of antiviral nu cleosides via hydrophobic amino acid phorphoramidate prodrugs. Synthetic methodologies have been developed for the construction of phosphoramidate amino acid nucleosides and biological and biochemical experiments have been conducted. The phosphomonoester amidates were shown to be water soluble and indefinitely stable in human blood. Several of the antiviral phosphoramidates have demonstrated greater potency than the parent nucleosides, but with little or no associated cytotoxicity toward human cell cultures or a.nimals. Mechanistic studies attempting to characterize the activity of these unique compounds have provided supporting evidence for direct intracellular P-N bond cleavage by T lymphocytes. In addition, using the rat as a model system, we have observed that amino acid phosphomonoester amidates of AZT have a significantly longer in vivo half life than the parent nucleoside, suggesting that phosphoramidates maybe able to significantly enhance the pharamcokinetic parameters for nucleoside based drugs from minutes to days.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

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nucleosides
Drug delivery
Nucleosides
Antiviral Agents
Nucleotides
nucleotides
Amino Acids
drugs
amino acids
T-cells
Prodrugs
Cytotoxicity
Cell culture
half life
Half-Life
cytotoxicity
Rats
cell culture
Blood
Cell Culture Techniques

Cite this

Wagner, C. R., McIntee, E. J., Chang, S. L., & Zimmerman, C. (1997). Antiviral nucleotide drug delivery via amino acid phosphoramidates. FASEB Journal, 11(9).

Antiviral nucleotide drug delivery via amino acid phosphoramidates. / Wagner, Carston R.; McIntee, Edward J.; Chang, Shu Ling; Zimmerman, Cheryl.

In: FASEB Journal, Vol. 11, No. 9, 01.12.1997.

Research output: Contribution to journalArticle

Wagner, CR, McIntee, EJ, Chang, SL & Zimmerman, C 1997, 'Antiviral nucleotide drug delivery via amino acid phosphoramidates', FASEB Journal, vol. 11, no. 9.
Wagner, Carston R. ; McIntee, Edward J. ; Chang, Shu Ling ; Zimmerman, Cheryl. / Antiviral nucleotide drug delivery via amino acid phosphoramidates. In: FASEB Journal. 1997 ; Vol. 11, No. 9.
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