Research Topics
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Publications
Dual mode of interaction of DNA polymerase epsilon with proliferating cell nuclear antigen in primer binding and DNA synthesisG Maga
Institute of Biochemical and Evolutionary Genetics IGBE CNR, National Research Council, via Abbiategrasso 207, Pavia, I 27100, Italy
J Mol Biol 285:259-67. 1999..The significance of this dual interaction is discussed with reference to the physiological roles of DNA polymerase epsilon and its interaction with the clamp proliferating cell nuclear antigen...
Molecular basis for the enantioselectivity of HIV-1 reverse transcriptase: role of the 3'-hydroxyl group of the L-(beta)-ribose in chiral discrimination between D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphate analogsG Maga
Institute of Biochemical and Evolutionary Genetics, National Research Council, I 27100, Pavia, Italy
Nucleic Acids Res 27:972-8. 1999....
Potentiation of inhibition of wild-type and mutant human immunodeficiency virus type 1 reverse transcriptases by combinations of nonnucleoside inhibitors and d- and L-(beta)-dideoxynucleoside triphosphate analogsG Maga
Istituto di Genetica Biochimica ed Evoluzionistica CNR, Universita degli Studi, I 27100 Pavia, Italy
Antimicrob Agents Chemother 45:1192-200. 2001....
Okazaki fragment processing: modulation of the strand displacement activity of DNA polymerase delta by the concerted action of replication protein A, proliferating cell nuclear antigen, and flap endonuclease-1G Maga
Istituto di Genetica Biochimica ed Evoluzionistica Consiglio Nazionale delle Ricerche, I 27100 Pavia, Italy
Proc Natl Acad Sci U S A 98:14298-303. 2001..Our data support a model for Okazaki fragment processing where the strand displacement activity of DNA polymerase delta is modulated by the concerted action of PCNA, RP-A and Fen 1...
Combinations against combinations: associations of anti-HIV 1 reverse transcriptase drugs challenged by constellations of drug resistance mutationsGiovanni Maga
Istituto di Genetica Biochimica ed Evoluzionistica IGBE CNR, Pavia, Italy
Curr Drug Metab 3:73-95. 2002..A major focus will be on the reciprocal influence of drug associations on their own metabolism as well as on the interacting effects of the selected combinations of drug resistance mutations...
DNA polymerase theta purified from human cells is a high-fidelity enzymeGiovanni Maga
Istituto di Genetica Molecolare IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
J Mol Biol 319:359-69. 2002..Our findings are discussed in light of the proposed physiological role of hpol theta...
Hepatitis C virus NS3 NTPase/helicase: different stereoselectivity in nucleoside triphosphate utilisation suggests that NTPase and helicase activities are coupled by a nucleotide-dependent rate limiting stepG A Locatelli
Istituto di Genetica Biochimica ed Evoluzionistica IGBE-CNR, Pavia, Italy
J Mol Biol 313:683-94. 2001..These observations provide an essential mechanistic background for the development of specific nucleotide analogs targeting either activity as potential anti-HCV agents...
HIV-1 reverse transcriptase inhibitors: current issues and future perspectivesG A Locatelli
DNA Enzymology and Molecular Virology, Istituto di Genetica Molecolare IGM-CNR, via Abbiategrasso 207, Pavia, Italy
Curr Drug Metab 5:283-90. 2004..This review will summarise the most recent achievements, as well as the future directions in the development of novel anti-RT compounds...
Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replicationA Garbelli
Institute of Molecular Genetics IGMCNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Curr Med Chem 18:3015-27. 2011....
Drug resistance mutations in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase differentially affect the phosphorolysis-dependent primer unblocking activity in the presence of stavudine and zidovudine and its inhibEmmanuele Crespan
IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy
Antimicrob Agents Chemother 49:342-9. 2005..e., drug resistance), the molecular mechanisms underlying this phenotype can be very different. Moreover, the same mutation can give rise to different phenotypes depending on the nature of the substrates and/or inhibitors...
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 complexGiada A Locatelli
Istituto di Genetica Molecolare IGM-CNR, Consiglio Nazionale delle Ricerche, 27100 Pavia, Italy
Antimicrob Agents Chemother 48:1570-80. 2004..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...
Non-nucleoside HIV-1 reverse transcriptase inhibitors di-halo-indolyl aryl sulfones achieve tight binding to drug-resistant mutants by targeting the enzyme-substrate complexAlberta Samuele
Department of DNA Enzymology and Molecular Virology, Institute of Molecular Genetics, National Research Council, IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Antiviral Res 81:47-55. 2009....
Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replicationStefania Paolucci
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy
Antimicrob Agents Chemother 48:4611-7. 2004..This finding may explain the lower frequency of Gln145Met/Leu mutations observed compared with the frequencies of Gln151Met/Leu mutations and the insertion at position 69 in HAART-experienced patients...
DNA polymerases and oxidative damage: friends or foes?A Amoroso
Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Curr Mol Pharmacol 1:162-70. 2008..In this review we will summarize the most recent advancements in the field of oxidative DNA damage tolerance with special emphasis on the pro- and anti-mutagenic roles of DNA pols and auxiliary proteins...
Vif is an auxiliary factor of the HIV-1 reverse transcriptase and facilitates abasic site bypassReynel Cancio
Istituto di Genetica Molecolare IGM - CNR, via Abbiategrasso 207, I-27100 Pavia, Italy
Biochem J 383:475-82. 2004..In addition, Vif was found to promote the bypass of an abasic site by HIV-1 RT...
Inhibition of mammalian DNA polymerases by resveratrol: mechanism and structural determinantsGiada A Locatelli
Istituto di Genetica Molecolare IGM-CNR, 27100 Pavia, Italy
Biochem J 389:259-68. 2005..Our findings establish the necessary background for the synthesis of resveratrol derivatives having more selective and potent antiproliferative activity...
Substrate-induced stable enzyme-inhibitor complex formation allows tight binding of novel 2-aminopyrimidin-4(3H)-ones to drug-resistant HIV-1 reverse transcriptase mutantsAlberta Samuele
Istituto di Genetica Molecolare IGM CNR via Abbiategrasso 207, 27100 Pavia, Italy
ChemMedChem 3:1412-8. 2008..Interestingly, one compound showed dissociation rates from the ternary complex with RT mutants K103N and Y181I 10-20-fold slower than from the corresponding complex with wild-type RT...
The block of DNA polymerase delta strand displacement activity by an abasic site can be rescued by the concerted action of DNA polymerase beta and Flap endonuclease 1Giovanni Maga
Institute of Molecular Genetics National Research Council, via Abbiategrasso 207, I 27100 Pavia, Italy
J Biol Chem 284:14267-75. 2009..Our data identify a previously unnoticed deleterious effect of the AP site lesion on normal cell metabolism and suggest the existence of a novel repair pathway that might be important in preventing replication fork stalling...
Detection of a new HIV-1 reverse transcriptase mutation (Q145M) conferring resistance to nucleoside and non-nucleoside inhibitors in a patient failing highly active antiretroviral therapyStefania Paolucci
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy
AIDS 17:924-7. 2003
8-oxo-guanine bypass by human DNA polymerases in the presence of auxiliary proteinsGiovanni Maga
Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Nature 447:606-8. 2007....
Overcoming the drug resistance problem with second-generation tyrosine kinase inhibitors: from enzymology to structural modelsE Crespan
Institute of Molecular Genetics IGMCNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Curr Med Chem 18:2836-47. 2011....
Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases beta and lambdaEmmanuele Crespan
Istituto di Genetica Molecolare, IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Nucleic Acids Res 35:45-57. 2007..Therefore, this NNTP analog can be considered as the prototype of an entirely novel class of DNA pol substrates...
Slow-, tight-binding HIV-1 reverse transcriptase non-nucleoside inhibitors highly active against drug-resistant mutantsReynel Cancio
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche via Abbiategrasso 207, 27100 Pavia, Italy
ChemMedChem 2:445-8. 2007
DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein AGiovanni Maga
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
J Biol Chem 280:1971-81. 2005....
Human DEAD-box ATPase DDX3 shows a relaxed nucleoside substrate specificityRaffaella Franca
DNA Enzymology and Molecular Virology Unit, Istituto di Genetica Molecolare IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Proteins 67:1128-37. 2007..Our results expand the knowledge about the DEAD-box RNA helicases in general and can be used for rational design of selective inhibitors of hDDX3, to be tested as potential antitumor and antiviral agents...
NNRTI-selected mutations at codon 190 of human immunodeficiency virus type 1 reverse transcriptase decrease susceptibility to stavudine and zidovudineStefania Paolucci
Servizio di Virologia, IRCCS Policlinico San Matteo, 27100 Pavia, Italy
Antiviral Res 76:99-103. 2007..Selection of double mutants, with further decrease in NRTI susceptibility, might be favoured by the compensatory effect of T215Y on the reduction of RT catalytic efficiency associated with G190S...
Selective targeting of the HIV-1 reverse transcriptase catalytic complex through interaction with the "primer grip" region by pyrrolobenzoxazepinone non-nucleoside inhibitors correlates with increased activity towards drug-resistant mutantsSamantha Zanoli
Institute of Molecular Genetics, IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Biochem Pharmacol 76:156-68. 2008..Molecular modeling and docking studies provided an explanation for this correlation at the structural level...
Slow binding-tight binding interaction between benzimidazol-2-one inhibitors and HIV-1 reverse transcriptase containing the lysine 103 to asparagine mutationAlberta Samuele
Department of DNA Enzymology and Molecular Virology, Institute of Molecular Genetics National Research Council, IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Antiviral Res 86:268-75. 2010....
Cell cycle-dependent dynamic association of cyclin/Cdk complexes with human DNA replication proteinsIsabelle Frouin
Istituto di Genetica Molecolare-CNR, Pavia, Italy
EMBO J 21:2485-95. 2002....
DNA polymerases and mutagenesis in human cancersEmmanuele Crespan
Istituto di Genetica Molecolare IGM CNR, Consiglio Nazionale delle Ricerche, I 27100 Pavia, Italy
Subcell Biochem 50:165-88. 2010..In this chapter, we present the role of each Pol in genome maintenance and highlight the connections between the malfunctioning of these enzymes and cancer progress...
Human DNA polymerase lambda diverged in evolution from DNA polymerase beta toward specific Mn(++) dependence: a kinetic and thermodynamic studyGiuseppina Blanca
Istituto di Genetica Molecolare IGM CNR, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
Biochemistry 42:7467-76. 2003....
Nevirapine-selected mutations Y181I/C of HIV-1 reverse transcriptase confer cross-resistance to stavudineFausto Baldanti
Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia, Italy
AIDS 17:1568-70. 2003..A previously unnoticed role of Y181I/C RT changes selected by nevirapine or other NNRTI in determining stavudine resistance is documented...
DNA replication: a complex matterIsabelle Frouin
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I-27100 Pavia, Italy
EMBO Rep 4:666-70. 2003..In this review, we summarize current knowledge about the composition and dynamics of these large multiprotein complexes in mammalian cells and their relationships to the replication factories...
Replication protein A and proliferating cell nuclear antigen coordinate DNA polymerase selection in 8-oxo-guanine repairGiovanni Maga
Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I 27100 Pavia, Italy
Proc Natl Acad Sci U S A 105:20689-94. 2008....
Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partnersIsabelle Frouin
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100 Pavia, Italy
J Biol Chem 278:39265-8. 2003..These observations suggest that PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair...
APOBEC deaminases as cellular antiviral factors: a novel natural host defense mechanismRaffaella Franca
Istituto di Genetica Molecolare IGM CNR, Pavia, Italy
Med Sci Monit 12:RA92-8. 2006..This article is aimed at broadening the current knowledge about the antiviral activity of the APOBEC members and to highlight the notion that their role(s) might be more general than previously anticipated...
Error-free bypass of 2-hydroxyadenine by human DNA polymerase lambda with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contextsEmmanuele Crespan
Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, I 27100 Pavia, Italy
Nucleic Acids Res 35:5173-81. 2007..Our data show, for the first time, that the 2-OH-A lesion can be efficiently and faithfully bypassed by a human DNA pol lambda in combination with PCNA and RP-A...
Discovery of non-nucleoside inhibitors of HIV-1 reverse transcriptase competing with the nucleotide substrateGiovanni Maga
Istituto di Genetica Molecolare, IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Angew Chem Int Ed Engl 46:1810-3. 2007
Dual Src and Abl inhibitors target wild type Abl and the AblT315I Imatinib-resistant mutant with different mechanismsEmmanuele Crespan
Institute of Molecular Genetics IGM CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Bioorg Med Chem 18:3999-4008. 2010....
Human replication protein A can suppress the intrinsic in vitro mutator phenotype of human DNA polymerase lambdaGiovanni Maga
Istituto di Genetica Molecolare, IGM CNR, Pavia, Italy
Nucleic Acids Res 34:1405-15. 2006..Possible physiological implications of these findings for the in vivo fidelity of pol lambda are discussed...
Diketo hexenoic acid derivatives are novel selective non-nucleoside inhibitors of mammalian terminal deoxynucleotidyl transferases, with potent cytotoxic effect against leukemic cellsGiada A Locatelli
Istituto di Genetica Molecolare IGM-CNR, via Abbiategrasso 207, 27100 Pavia, Italy
Mol Pharmacol 68:538-50. 2005..9 muM), thus having the potential to be further developed as a novel antitumor agent...
High potency of indolyl aryl sulfone nonnucleoside inhibitors towards drug-resistant human immunodeficiency virus type 1 reverse transcriptase mutants is due to selective targeting of different mechanistic forms of the enzymeReynel Cancio
Istituto di Genetica Molecolare IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy
Antimicrob Agents Chemother 49:4546-54. 2005....
Nevirapine resistance mutation at codon 181 of the HIV-1 reverse transcriptase confers stavudine resistance by increasing nucleotide substrate discrimination and phosphorolytic activityGiuseppina Blanca
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, I-27100 Pavia, Italy
J Biol Chem 278:15469-72. 2003..These results reveal a new mechanism for cross-resistance between different classes of HIV-1 RT inhibitors...
Mutagenesis of human DNA polymerase lambda: essential roles of Tyr505 and Phe506 for both DNA polymerase and terminal transferase activitiesIgor Shevelev
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057, Zurich, Switzerland
Nucleic Acids Res 31:6916-25. 2003..Our results suggest the existence of a common nucleotide-binding site for the polymerase and terminal transferase activities of pol lambda, as well as distinct roles of the amino acids Tyr505 and Phe506 in these two catalytic functions...
Human base excision repair complex is physically associated to DNA replication and cell cycle regulatory proteinsEleonora Parlanti
Department of Environment and Primary Prevention, Section of Molecular Epidemiology, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
Nucleic Acids Res 35:1569-77. 2007..This finding suggests that a preassembled DNA repair machinery is constitutively active in cycling cells and is ready to be recruited at base damage and breaks occurring at replication forks...
Replication of 2-hydroxyadenine-containing DNA and recognition by human MutSalphaFlavia Barone
Unit of Experimental Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
DNA Repair (Amst) 6:355-66. 2007..MutSalpha also recognized 2-OH-A located in a repeat sequence that mimics a frameshift intermediate...
Specific targeting highly conserved residues in the HIV-1 reverse transcriptase primer grip region. Design, synthesis, and biological evaluation of novel, potent, and broad spectrum NNRTIs with antiviral activityCaterina Fattorusso
Dipartimento di Chimica delle Sostanze Naturali, Universita' di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy
J Med Chem 48:7153-65. 2005..Among the pyrrolobenzoxazepines investigated, 15c appeared to be the most promising NNRTI of the series characterized by potent antiviral activity, broad spectrum, and low cytotoxicity. 15c showed synergistic antiviral activity with AZT...
Human DNA polymerase lambda possesses terminal deoxyribonucleotidyl transferase activity and can elongate RNA primers: implications for novel functionsKristijan Ramadan
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
J Mol Biol 328:63-72. 2003..These two novel properties of human DNA polymerase lambda might suggest additional roles for this enzyme in DNA replication and repair processes...
Eukaryotic DNA polymerasesUlrich Hubscher
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
Annu Rev Biochem 71:133-63. 2002..These are the lesion-replicating enzymes pol zeta, pol eta, pol iota, pol kappa, and Rev1, and a group of pols called pol theta;, pol lambda, pol micro, pol sigma, and pol phi that fulfill a variety of other tasks...
Human DNA polymerases lambda and beta show different efficiencies of translesion DNA synthesis past abasic sites and alternative mechanisms for frameshift generationGiuseppina Blanca
Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 205 route de Narbonne, 31077 Toulouse Cedex, France
Biochemistry 43:11605-15. 2004....
Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases beta and lambdaEmmanuele Crespan
Istituto di Genetica Molecolare IGM-CNR via Abbiategrasso 207, I-27100 Pavia, Italy
Nucleic Acids Res 33:4117-27. 2005..These results show for the first time that neither the base nor the sugar moieties of nucleotides are required for incorporation by family X DNA polymerases...
Repair and translesion DNA polymerases as anticancer drug targetsGiovanni Maga
Ulrich Hübscher Institute for Veterinary Biochemistry and Molecular Biology, University of Zurich Irchel, Winterthurerstrasse 190, Zurich, Switzerland
Anticancer Agents Med Chem 8:431-47. 2008..In this review we will concentrate on DNA repair proteins and translesion DNA polymerases as possible targets for anti cancer drugs...
De novo DNA synthesis by human DNA polymerase lambda, DNA polymerase mu and terminal deoxyribonucleotidyl transferaseKristijan Ramadan
Institute of Veterinary Biochemistry and Molecular Biology, , Winterthurerstrasse 190, CH-8057, , Switzerland
J Mol Biol 339:395-404. 2004..This novel catalytic activity might be related to the proposed functions of these three pol X family members in DNA repair and DNA recombination...
Investigation of novel lipid-functionalized PNA monomers as potential HIV-1 non-nucleoside reverse transcriptase and/or integrase inhibitorsMichael G Thomas
Chemistry, School of Engineering and Physical Sciences, Heriot Watt University, Edinburgh, United Kingdom
Nucleosides Nucleotides Nucleic Acids 26:1063-6. 2007..A range of novel N-terminal lipid-functionalized peptide nucleic acid (PNA) monomers have been prepared and their abilities to inhibit HIV-1 reverse transcriptase and integrase have been examined...
Novel N1-substituted 1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside reverse transcriptase inhibitorsAnna Maria Monforte
Dipartimento Farmaco Chimico, Universita di Messina, Viale Annunziata, 98168 Messina, Italy
Bioorg Med Chem 16:7429-35. 2008..SAR studies highlighted that the nature of the substituents at N(1) and on the benzene ring of benzimidazolone moiety significantly influenced the anti-HIV activity of this class of potent antiretroviral agents...
5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure-activity relationship profileMaxim B Nawrozkij
Volgograd State Technical UniVersity, Pr Lenina, 28, 400131 Volgograd, Russia
J Med Chem 51:4641-52. 2008..These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs...
Synthesis and biological investigation of S-aryl-S-DABO derivatives as HIV-1 inhibitorsClaudia Mugnaini
Dipartimento Farmaco Chimico Tecnologico, , Via De Gasperi, 2 I-53100 Siena, Italy
Bioorg Med Chem Lett 16:3541-4. 2006..The results of their evaluation as inhibitors of RT are reported together with their antiviral activity in cellular assays...
Selective interactions of human kin17 and RPA proteins with chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated mannerLaurent Miccoli
Commissariat a l Energie Atomique, Direction des Sciences du Vivant, Laboratoire de Génétique de la Radiosensibilité, Departement de Radiobiologie et de Radiopathologie, F 92265 Fontenay aux Roses, France
Nucleic Acids Res 31:4162-75. 2003....
A new and efficient synthesis of substituted 6-[(2'-dialkylamino)ethyl] pyrimidine and 4-N,N-dialkyl-6-vinyl-cytosine derivatives and evaluation of their anti-rubella activityRaffaele Saladino
Unita INFM, Dipartimento Agrochimico Agrobiologico, Universita della Tuscia, Via San Camillo De Lellis, 01100 Viterbo, Italy
Bioorg Med Chem 10:2143-53. 2002..Among the new derivatives obtained, various compounds show anti-Rubella activity. The inhibition of HIV-1 Reverse Transcriptases (RT), from both wild type and modified viruses, is also reported...
Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: past, present, and future perspectivesGiuseppe Campiani
Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Via Aldo Moro, 53100 Siena, Italy
Curr Pharm Des 8:615-57. 2002..Starting from the first generation, this review will focus on the second generation NNRTIs dealing with the recent and most interesting published results, highlighting the guidelines for the development of a third generation of NNRTIs...
DNA polymerase lambda from calf thymus preferentially replicates damaged DNAKristijan Ramadan
Institute of Veterinary Biochemistry and Molecular Biology, , Winterthurerstrasse 190, CH-8057, , Switzerland
J Biol Chem 277:18454-8. 2002..The biochemical properties of the calf thymus DNA polymerase lambda, described here for the first time, are discussed in relationship to the proposed role for this DNA polymerase in vivo...
Dihydro-alkylthio-benzyl-oxopyrimidines as inhibitors of reverse transcriptase: synthesis and rationalization of the biological data on both wild-type enzyme and relevant clinical mutantsClaudia Mugnaini
Dipartimento Farmaco Chimico Tecnologico, Universita degli Studi di Siena, Via Alcide de Gasperi 2, I 53100 Siena, Italy
J Med Chem 50:6580-95. 2007....
The balance between the rates of incorporation and pyrophosphorolytic removal influences the HIV-1 reverse transcriptase bypass of an abasic site with deoxy-, dideoxy-, and ribonucleotidesBechan Sharma
Department of Biochemistry, University of Allahabad, Allahabad, India
Proteins 71:715-27. 2008..We find that AP sites can substantially influence the substrate specificity of HIV-1 RT and that pyrophosphorolysis plays a significant role in determining the ability of HIV-1 RT to (mis)incorporate nucleotides...
Parallel solution-phase and microwave-assisted synthesis of new S-DABO derivatives endowed with subnanomolar anti-HIV-1 activityFabrizio Manetti
Dipartimento Farmaco Chimico Tecnologico, , Via Alcide de Gasperi 2, I-53100 Siena, Italy
J Med Chem 48:8000-8. 2005....
Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamideRino Ragno
Dipartimento di Studi Farmaceutici, Istituto Pasteur Fondazione Cenci Bolognetti, Universita di Roma La Sapienza, Piazzale Aldo Moro 5, I 00185 Roma, Italy
J Med Chem 49:3172-84. 2006..These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages...
Design, synthesis, biological evaluation, and molecular modeling studies of TIBO-like cyclic sulfones as non-nucleoside HIV-1 reverse transcriptase inhibitorsRoberto Di Santo
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, P le A Moro 5, 00185 Roma, Italy
ChemMedChem 1:82-95. 2006..Predictive 3D QSAR models were obtained with a receptor-based alignment by docking of TIBO- and TBO-like derivatives into the NNBS of RT...
Human terminal deoxynucleotidyl transferases as novel targets for anticancer chemotherapyRoberto Di Santo
Istituto Pasteur-Fondazione Cenci Bolognetti, Dip. di Studi Farmaceutici, , , Italy
Curr Med Chem 13:2353-68. 2006..In this review, we will summarize the recent advances in the synthesis and characterization of the first classes of specific inhibitors of mammalian terminal transferases and their potential applications...
Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamideGabriella De Martino
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, , Roma, Italy
Antivir Chem Chemother 17:59-77. 2006..A cross-docking study was also undertaken to gain some insights in to the binding mode of the newly synthesized IASs in the wt and mutated isoforms of reverse transcriptase...
Arylthiopyrrole (AThP) derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis, structure-activity relationships, and docking studies (part 1)Roberto Di Santo
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, P le A Moro 5, 00185 Roma, Italy
ChemMedChem 1:1367-78. 2006..Docking calculations were also performed to investigate the binding mode of compounds 2, 4e, 4j, 4k and 5e into the non-nucleoside binding site of HIV-1 RT and to rationalize some structure-activity relationships and resistance data...
Structure-based pharmacophore identification of new chemical scaffolds as non-nucleoside reverse transcriptase inhibitorsMaria Letizia Barreca
Dipartimento Farmaco Chimico, Universita di Messina, Viale Annunziata, 98168 Messina, Italy
J Chem Inf Model 47:557-62. 2007..The positive biological results obtained confirm the validity of our work strategy...
Discovery of novel benzimidazolones as potent non-nucleoside reverse transcriptase inhibitors active against wild-type and mutant HIV-1 strainsMaria Letizia Barreca
Dipartimento Farmaco Chimico, Universita di Messina, Viale Annunziata, 98168 Messina, Italy
Bioorg Med Chem Lett 17:1956-60. 2007..It is worth noting that compound 3 proved to have antiretroviral activity similar to that of efavirenz and greater than that of nevirapine, two of the three NNRTIs currently available in antiretroviral therapy...
8-oxoguanine incorporation into DNA repeats in vitro and mismatch recognition by MutSalphaPeter MacPherson
Cancer Research UK London Research Institute, Clare Hall Laboratories South Mimms, Herts, EN6 3LD, UK
Nucleic Acids Res 33:5094-105. 2005..These findings are consistent with a contribution of oxidative DNA damage to frameshifts. They also suggest how mismatch repair might reduce the burden of DNA 8-oxoG and prevent frameshift formation...
Novel 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. A structure-activity relationship investigationGabriella De Martino
Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, , Piazzale Aldo Moro 5, I-00185 Roma, Italy
J Med Chem 48:4378-88. 2005..Compounds 7 (ID(50) = 8.25 microM) were found more active than efavirenz (ID(50) = 25 microM) against the viral RT carrying the K103N mutation, suggesting for these compounds a potential use in efavirenz based anti-AIDS regimens...
N2-benzyloxycarbonylguan-9-yl acetic acid derivatives as HIV-1 reverse transcriptase non-nucleoside inhibitors with decreased loss of potency against common drug-resistance mutationsKassim F Adebambo
Chemistry Department, School of Engineering and Physical Sciences, Heriot-Watt University, William H. Perkin Building, Riccarton, Edinburgh EH14 4AS, UK
ChemMedChem 2:1405-9. 2007
Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RTMaria Letizia Barreca
Dipartimento Farmaco-Chimico, , Viale Annunziata, 98168 Messina, Italy. barreca@ pharma.unime.it
J Med Chem 48:3433-7. 2005..Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs...
5-Alkyl-2-alkylamino-6-(2,6-difluorophenylalkyl)-3,4-dihydropyrimidin-4(3H)-ones, a new series of potent, broad-spectrum non-nucleoside reverse transcriptase inhibitors belonging to the DABO familyAntonello Mai
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, P le A Moro 5, I 00185 Roma, Italy
Bioorg Med Chem 13:2065-77. 2005....
Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strainsAntonello Mai
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universita degli Studi di Roma La Sapienza, P le A Moro 5, 00185 Roma, Italy
J Med Chem 50:5412-24. 2007..The higher inhibitor adaptability to the HIV-1 RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs...
Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activityGiuseppe La Regina
Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Sapienza Universita di Roma, Piazzale Aldo Moro 5, I 00185 Roma, Italy
J Med Chem 50:5034-8. 2007..Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations...
