New Reverse Transcriptase Inhibitors

Crowe, Suzanne

doi:10.1007/978-1-4615-4743-3_18

Cited by 10 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major mechanism of their antiviral action is the inhibition of virus-induced DNA polymerases [2] or reverse transcriptases [3,4]. ANPs thus inhibit replication of both DNA viruses and retroviruses including HIV.…”

Section: Introductionmentioning

confidence: 99%

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3

et al. 2006

View full text Add to dashboard Cite

Acyclic nucleoside phosphonates are potent antiviral agents effective against replication of DNA viruses and retroviruses including human immunodeficiency virus (HIV). In addition to their antimetabolic mode of antiviral action, acyclic nucleoside phosphonates also possess immunomodulatory properties. We have shown recently that a number of them stimulate secretion of cytokines including chemokines RANTES/CCL5 ("regulated upon activation, normal T cell expressed and secreted") and MIP-1 alpha/CCL3 (macrophage inflammatory protein-1 alpha) that may inhibit entry of HIV in cells. In present experiments we analyzed effects of acyclic nucleoside phosphonates on gene expression of other members of the beta family of chemokines, monocyte chemotactic proteins (MCPs), which have also been implicated in the control of HIV infection. The following compounds differing at the type of heterocyclic base, i.e. adenine (A), or 2,6-diaminopurine (DAP), at the 6-amino group of the base, and at the N ( 9 )-side chain represented by 9-[2-(phosphonomethoxy)ethyl] (PME) and 9-[2-(phosphonomethoxy)propyl] (PMP) moieties were included in the study: (1) (R)-PMPA, ie. tenofovir, (2) N ( 6 )-cyclopropyl-(R)-PMPDAP, (3) N ( 6 )-cyclopentyl-(R)-PMPDAP, (4) N ( 6 )-dimethylaminoethyl-(R)-PMPDAP, (5) N ( 6 )-cyclopentyl-PMEDAP, (6) N ( 6 )-isobutyl-PMEDAP, (7) N ( 6 ) -cyclohexylmetyl-PMEDAP, and (8) N ( 6 ) -cyclooctyl-PMEDAP. These compounds are able to activate production of MCP-1 and MCP-3, and none of them influences gene expression of MCP-2, and MCP-5. Enhancement of monocyte chemotactic protein expression was found to be mediated by transcriptional factor nuclear factor-kappaB (NF-kappaB).

show abstract

Section: Introductionmentioning

confidence: 99%

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3

et al. 2006

View full text Add to dashboard Cite

show abstract

“…When plants are subjected to low temperature stress, a large amount of ROS will be produced, which can participate in various metabolisms and is the second messenger regulating cell growth and death. In a normal growth environment, ROS should be in a state of dynamic equilibrium in the plant; under low temperature stress, the large amount of ROS production will cause a series of biochemical reactions such as DNA damage, protein inactivation, cell membrane peroxidation and even cell dysfunction and death [46]. This is when the plant's antioxidant enzyme scavenging system comes into play, showing appropriate stress response to regulate reactive oxygen species and free radical levels as a means of protecting the plant.…”

Section: Mechanism For Improving Low Temperature Tolerance Of Grafted...mentioning

confidence: 99%

Study on the Mechanism of Grafting to Improve the Tolerance of Pepper to Low Temperature

Long

Suo

et al. 2023

Agronomy

View full text Add to dashboard Cite

Pepper is a horticultural crop that does not tolerate low temperatures. To investigate how the grafted pepper responds to low temperature stress in the short term, transcriptome analysis was performed on grafted seedlings treated with low temperature for 1 h, 4 h, 12 h and 24 h compared with those treated for 0 h. The results showed that genes related to CAM4, MPK8, RbohD and OXI1 might be related to the response of grafted seedlings to low temperature stress in the short term. To investigate how low temperature tolerant rootstocks can improve the low temperature tolerance of grafted peppers, morphological and physiological indices of self-rooted and grafted seedlings were analyzed under low temperature conditions for different days. The results showed that the degree of wilting, REL and MDA content of grafted seedlings were significantly lower than those of self-rooted seedlings, and the antioxidant enzyme activities were significantly higher than those of self-rooted seedlings under low temperature stress. The results indicated that grafted pepper would activate ROS-related genes in a short period of time after low temperature stress and produce a large amount of ROS in response to the low temperature stress. When ROS accumulated to a certain level, the grafted pepper could increase the enzyme activity of antioxidant system to remove the ROS produced in the body, and help the pepper seedlings adapt to low temperature stress through osmoregulation mechanism, so as to resist the damage caused by low temperature. The results of the study provide ideas for growing pepper in low temperature environment.

show abstract

“…Two classes of inhibitors are targeted to the viral RT: nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs) (9,11,28). The latter compounds are highly specific for HIV-1 RT and bind to the enzyme at an allosteric site close distinct from the catalytic site, behaving as typical noncompetitive inhibitors with respect to the different substrates of the polymerization reaction (12,23).…”

mentioning

confidence: 99%

Effects of Drug Resistance Mutations L100I and V106A on the Binding of Pyrrolobenzoxazepinone Nonnucleoside Inhibitors to the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Catalytic Complex

Locatelli

Campiani²,

Cancio

et al. 2004

Antimicrob Agents Chemother

View full text Add to dashboard Cite

). In order to better understand the structural basis for this selectivity, we exploited some PBO analogs characterized by various substituents at C-3 and by different inhibition potencies and drug resistance profiles, and we studied their interaction with HIV-1 RT wild type or carrying the drug resistance mutations L100I and V106A. Our kinetic and thermodynamic analyses showed that the formation of the complex between the enzyme and the nucleotide increased the inhibition potency of the compound PBO354 and shifted the free energy (energy of activation, ⌬G # ) for inhibitor binding toward more negative values. The V106A mutation conferred resistance to PBO 354 by increasing its dissociation rate from the enzyme, whereas the L100I mutation mainly decreased the association rate. This latter mutation also caused a severe reduction in the catalytic efficiency of the RT. These results provide a correlation between the efficiency of nucleotide utilization by RT and its resistance to PBO inhibition.

show abstract

New Reverse Transcriptase Inhibitors

Cited by 10 publications

References 35 publications

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3

Acyclic nucleoside phosphonate antivirals activate gene expression of monocyte chemotactic protein 1 and 3

Study on the Mechanism of Grafting to Improve the Tolerance of Pepper to Low Temperature

Effects of Drug Resistance Mutations L100I and V106A on the Binding of Pyrrolobenzoxazepinone Nonnucleoside Inhibitors to the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Catalytic Complex

Contact Info

Product

Resources

About