HIV‐1 Reverse transcriptase is capable of elongating derivatives of sequence specific noncomplementary oligodeoxynucleotides

Martyanov, Igor V.; Zakharova, O. D.; Sottofattori, Enzo; Maksakova, G. A.; Pyshnyi, D. V.; Mazzei, Mauro; Balbi, Alessandro; Litvak, Simón; Tarragó-Litvak, Laura; Nevinsky, Georgy A.

doi:10.1002/iub.7510450502

Cited by 5 publications

(5 citation statements)

References 7 publications

(9 reference statements)

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“…After addition of a ddT-unit to the 3′-terminal end of the ODN, some of these primers became very effective inhibitors of RT with Ki values in the nanomolar range. Martyanov et al [29] have carried out a comparison of Km and Vmax values for various primers in the polymerization reaction catalyzed by the HIV-1 RT. The affinity of RT for complementary d(pT)6 containing two different 5′-end pyranone derivatives was two to three orders of magnitude higher (Km = 3–15 nM) than that of d(pT)6 (Km = 12.6 mM).…”

Section: Introductionmentioning

confidence: 99%

Structure‐Activity Relationships of Synthetic Coumarins as HIV‐1 Inhibitors

Kostova¹,

Raleva

Genova

et al. 2006

Bioinorganic Chemistry and Applications

130

104

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HIV/AIDS pandemics is a serious threat to health and development of mankind, and searching for effective anti-HIV agents remains actual. Considerable progress has been made in recent years in the field of drug development against HIV. A lot of structurally different coumarins were found to display potent anti-HIV activity. The current review demonstrates the variety of synthetic coumarins having unique mechanism of action referring to the different stages of HIV replication. Recent studies based on the account of various synthetic coumarins seem to indicate that some of them serve as potent non-nucleoside RT-inhibitors, another as inhibitors of HIV-integrase or HIV-protease. The merits of selecting potential anti-HIV agents to be used in rational combination drugs design and structure-activity relationships are discussed.The scientific community is looking actively for new drugs and combinations for treatment of HIV infection effective for first-line treatment, as well as against resistant mutants. The investigation on chemical anti-HIV agents gives hope and optimism about it. This review article describes recent progress in the discovery, structure modification, and structure-activity relationship studies of potent anti-HIV coumarin derivatives.

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Section: Introductionmentioning

confidence: 99%

Structure‐Activity Relationships of Synthetic Coumarins as HIV‐1 Inhibitors

Kostova¹,

Raleva

Genova

et al. 2006

Bioinorganic Chemistry and Applications

130

104

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“…We have reported preliminary results showing that the presence of three coumarinor chromone-related derivatives in different ODNs enhanced the interaction with HIV-1 RT (Martyanov et al, 1998). Here, we extend these results to 10 different derivatives, and further analyzed how these polycyclic compounds can affect the capacity of noncomplementary ODNs to be used as primers.…”

Section: Inhibition Of Rt By Odn Derivativesmentioning

confidence: 59%

Interaction of Oligonucleotides Conjugated to Substituted Chromones and Coumarins with HIV-1 Reverse Transcriptase

Martyanov¹,

Zakharova²,

Sottofattori³

et al. 1999

Antisense and Nucleic Acid Drug Development

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Ten different pyranone-related substituents (chromones or coumarins) were covalently linked to the 5' end of various oligonucleotides (ODN). The interaction of these compounds with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) was analyzed. A different behavior was found to depend on the structure of the oligonucleotide derivatives. Some compounds activated the enzyme at relatively low concentrations (0.1-0.5 microM), followed by an inhibition of the activity at higher concentrations (5-20 microM), whereas others behave just as inhibitors. Because the presence of some coumarin or chromone derivatives conjugated to ODNs enhanced the interaction with the reverse transcriptase, we analyzed the capacity of such ODN derivatives to be used as primers. The introduction of substituent I, a chromone derivative, the 2-[(3-(aminopropyl)amino]-8-isopropyl-5-methyl-4-oxo-4H-1-benzopyran-3-c arbaldehyde], and II, a coumarin derivative, the 1-(3-aminopropoxy)-2-ethyl-3H-naphto[2,1-b]pyran-3-one, into the 5' end of a noncomplementary ODN allowed these compounds to be used as primers. In the case of complementary primers, the presence of conjugated derivatives enhanced the affinity with Km values that were two to three orders of magnitude lower than that of a complementary primer of the same length. After addition of a ddT-unit to the 3'-terminal end of the ODN, some of these primers became very effective inhibitors of RT with Ki values in the nanomolar range.

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“…Some compounds activated the enzyme at relatively low concentrations (0.1-0.5 μM), followed by an inhibition of the activity at higher concentrations (5-20 μM), whereas others behaved just as inhibitors. Because the presence of some coumarin or chromone derivatives conjugated to ODNs enhanced the interaction with the reverse transcriptase, Martyanov I. V. et al [62,63] analyzed the capacity of such ODN derivatives to be used as primers. The introduction of a chromone derivative, the 2-[(3-(aminopropyl)amino]-8-isopropyl-5-methyl-4-oxo-4H-1-benzopyran-3-c arbaldehyde], and a coumarin derivative, the 1-(3-aminopropoxy)-2-ethyl-3H-naphto[2,1-b]pyran-3-one, into the 5' end of a noncomplementary ODN allowed these compounds to be used as primers.…”

Section: Synthetic Coumarinsmentioning

confidence: 99%

“…After addition of a ddT-unit to the 3'-terminal end of the ODN, some of these primers became very effective inhibitors of RT with Ki values in the nanomolar range. The primer function of derivatives of noncomplementary ODNs appears to be due to the additional interactions of their 5'-terminal groups with the enzyme tRNA-binding site [62].…”

Section: Synthetic Coumarinsmentioning

confidence: 99%

Coumarins as Inhibitors of HIV Reverse Transcriptase

Kostova

2006

CHR

147

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Acquired immunodeficiency syndrome (AIDS), a degenerative disease of the immune and central nervous systems, is an enormous world-wide health threat. No cure has been found, and research is aimed at developing chemotherapy against the causative agent, human immunodeficiency virus (HIV). Chemotherapy for AIDS has progressed steadily in the past decade. However, new, effective, and less toxic chemotherapeutic agents are still needed. Plants, particularly anti-infective or immunomodulating herbal medicines, can serve as sources of new active leads to be further developed as anti-AIDS drug candidates. A lot of structurally different natural coumarins were found to display potent anti-HIV activity and continued progress is anticipated in the discovery of new leads and in the development of these agents as potential anti-AIDS drug candidates. Recent studies based on the account of various coumarins from plant sources and their analogs--synthetic coumarins, indicate that some of them serve as potent nonnucleoside RT-inhibitors, another as inhibitors of HIV-integrase or HIV-protease. The current review demonstrates the variety of coumarins of natural plant origin and synthetic coumarins having unique mechanism of action to one of the most important stage of HIV replication (RT-inhibition). The merits of selecting potential anti-HIV agents to be used in rational combination drugs design and structure-activity relationships are discussed. The scientific community is looking actively for new drugs and combinations for treatment of HIV infection effective for first-line treatment, as well as against drug-resistant mutants.

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HIV‐1 Reverse transcriptase is capable of elongating derivatives of sequence specific noncomplementary oligodeoxynucleotides

Cited by 5 publications

References 7 publications

Structure‐Activity Relationships of Synthetic Coumarins as HIV‐1 Inhibitors

Structure‐Activity Relationships of Synthetic Coumarins as HIV‐1 Inhibitors

Interaction of Oligonucleotides Conjugated to Substituted Chromones and Coumarins with HIV-1 Reverse Transcriptase

Coumarins as Inhibitors of HIV Reverse Transcriptase

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