Author
Tam Huynh-Dinh
Other affiliations: Centre national de la recherche scientifique, Polytechnic University of Catalonia, Pasteur Institute of Lille
Bio: Tam Huynh-Dinh is an academic researcher from Pasteur Institute. The author has contributed to research in topics: Nuclear magnetic resonance spectroscopy & Proton NMR. The author has an hindex of 29, co-authored 123 publications receiving 2828 citations. Previous affiliations of Tam Huynh-Dinh include Centre national de la recherche scientifique & Polytechnic University of Catalonia.
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TL;DR: It is proposed that the single base-pair opening event characterized here may be the only mode of base- Pair disruption, at temperatures well below the melting transition, and that catalyzed imino proton exchange is at this time the safest and most powerful, if not the only probe ofbase-pair kinetics.
193 citations
TL;DR: The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety.
Abstract: A new set of molecules made of an intercalating agent (oxazolopyridocarbazole, OPC) covalently linked through a polymethylene chain of various length to the 3' end of alpha-anomeric or beta-anomeric tetradeoxynucleotides (alpha- or beta-T4) have been synthesized The beta-thymidylate modified compound (beta-T4C5OPC) is able to interact with the complementary sequence, beta-poly (rA); this interaction is strongly stabilized compared to the parent compound, beta-oligo(dT)4 and is specific for poly (rA) The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety The stoechiometry of the binding reaction shows that an A-T pairing occurs in the alpha-beta heterohybrids Tm studies reveal that the alpha-beta heterohybrids are more stable than their beta-beta counterparts
157 citations
TL;DR: A mechanism of action for NCp7 in virus morphogenesis and replication is proposed from these results, which could facilitate the design of possible antiviral agents acting by a new mechanism.
139 citations
TL;DR: Correlation of the NMR data with molecular models has disclosed an equilibrium between several kinked conformations and has ruled out an unkinked structure of the double-stranded decanucleotide d(GCCG*G*ATCGC).
Abstract: A conformational study of the double-stranded decanucleotide d(GCCG*G*ATCGC).d(GCGATCCGGC), with the G* guanines chelating a cis-Pt(NH3)2 moiety, has been accomplished using 1H and 31P NMR, and molecular mechanics. Correlation of the NMR data with molecular models has disclosed an equilibrium between several kinked conformations and has ruled out an unkinked structure. The deformation is localized at the CG*G*.CCG trinucleotide where the helix is kinked by approximately 60 degrees towards the major groove and unwound by 12-19 degrees. The models revealed an unexpected mobility of the cytosine complementary to the 5'-G*. This cytosine can stack on either branch of the kinked complementary strand. The energy barrier between the two positions has been calculated to be less than or equal to 12 kJ/mol. The NMR data are in support of rapid flip-flopping of this cytosine. An explanation for the strong downfield shift observed in the 31P resonance of the G*pG* phosphate is given.
100 citations
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2,719 citations
TL;DR: Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.
Abstract: Modern drug discovery often involves screening small molecules for their ability to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused libraries), can be planned effectively with retrosynthetic analysis. Drug discovery can also involve screening small molecules for their ability to modulate a biological pathway in cells or organisms, without regard for any particular protein target. This process is likely to benefit in the future from an evolving forward analysis of synthetic pathways, used in diversity-oriented synthesis, that leads to structurally complex and diverse small molecules. One goal of diversity-oriented syntheses is to synthesize efficiently a collection of small molecules capable of perturbing any disease-related biological pathway, leading eventually to the identification of therapeutic protein targets capable of being modulated by small molecules. Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.
2,229 citations
TL;DR: The parmbsc0 force field as mentioned in this paper is a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the a/g concerted rotation in nucleic acids (NAs).
1,982 citations
TL;DR: Although annexins lack signal sequences for secretion, some members of the family have also been identified extracellularly where they can act as receptors for serum proteases on the endothelium as well as inhibitors of neutrophil migration and blood coagulation.
Abstract: Annexins are Ca2+ and phospholipid binding proteins forming an evolutionary conserved multigene family with members of the family being expressed throughout animal and plant kingdoms. Structurally,...
1,830 citations