Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several N-(S)-(3-hydroxy-2-phosphonylmethoxypropyl) (HPMP) and N-(2-phosphonylmethoxyethyl) (PME) derivatives of purine bases (adenine, guanine, 2-aminoadenine, 3-deazaadenine) and cytosine inhibit the growth of various DNA viruses. PME-derivatives (PMEA, PMEG and PMEDAP) are also active against retroviruses. Both types of nucleotide analogues undergo phosphorylation by cellular nucleotide kinases to their mono- and diphosphates. The phosphorylation with crude extracts of L-1210 cells is potentiated by an ATP-regenerating system. HPMPA is phosphorylated faster than PMEA with or without the ATP-regenerating system. The HPMP and PME analogues inhibit several virus-encoded target enzymes and their cellular counterparts: (1) HSV-1 DNA polymerase is inhibited by the diphosphates of the PME series; the virus-encoded enzyme is more sensitive than HeLa DNA pol alpha and beta. PMEApp terminates the growing DNA chain; it specifically replaces dATP. HPMPApp also acts as an alternative substrate of dATP, but, in contrast with PMEApp, it permits limited chain growth. (2) Diphosphates of both series inhibit HSV-1 ribonucleotide reductase; the greatest inhibition of CDP reduction to dCDP is exhibited by HPMPApp and PMEApp. The enzyme isolated from a PMEA-resistant HSV-1 mutant proved less sensitive to PMEApp, hydroxyurea and HPMPApp. (3) Diphosphates of PME derivatives efficiently inhibit AMV(MAV) reverse transcriptase. (4) The purine HPMP and PME analogues and, even more so, their monophosphate derivatives inhibit purine nucleoside phosphorylase from L-1210 cells.
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PMID:Acyclic nucleotide analogues: synthesis, antiviral activity and inhibitory effects on some cellular and virus-encoded enzymes in vitro. 169 93

A chemical structure is a joy forever, and this is how I perceived the chemical structures of a number of antiviral compounds with which I have been personally acquainted over the past 3 decades: (1) amino acid esters of acyclovir (i.e. valaciclovir); (2) 5-substituted 2'-deoxyuridines (i.e. brivudin); (3) 2',3'-dideoxynucleoside analogues (i.e. stavudine); (4) acyclic nucleoside phosphonates (ANPs) (i.e. cidofovir, adefovir); (5) tenofovir disoproxil fumarate (TDF) and drug combinations therewith; (6) tenofovir alafenamide (TAF, GS-7340), a new phosphonoamidate prodrug of tenofovir; (7) pro-prodrugs of PMEG (i.e. GS-9191 and GS-9219); (8) new ANPs: O-DAPy and 5-aza-C phosphonates; (9) non-nucleoside reverse transcriptase inhibitors (NNRTIs): HEPT and TIBO derivatives; and (10) bicyclam derivatives (i.e. AMD3100).
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PMID:Dancing with chemical formulae of antivirals: a personal account. 2387 44