Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

Rodríguez-Pérez, Tatiana; Fernández, Susana; Sanghvi, Yogesh S.; Detorio, Mervi; Schinazi, Raymond F.; Gotor, Vicente; Ferrero, Miguel

doi:10.1021/bc1002168

Cited by 16 publications

(9 citation statements)

References 49 publications

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“…The study of the substitution reactions of this Co III complex with related biologically relevant ligands with nitrogen donors, i.e., nucleosides or nucleobases, was further intended. Given the limitations in solubility of the nucleobases in this pH range, , as well as the blocking of one of the nitrogen donors of the base by the sugar unit, nucleosides were the choice. In fact, inosine has already been studied as a substituent species on cis -[Co(cyclen)(H 2 O) 2 ] 3+ in a very wide pH range .…”

Section: Resultsmentioning

confidence: 99%

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Martı́nez

Vázquez

2015

Inorg. Chem.

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The solution chemistry of complex [Co{(Me)2(μ-ET)cyclen}(H2O)2](3+) containing a fully substituted tetraammine ligand designed for the avoidance of base-conjugated substitution mechanisms in the 6-8 pH range has been studied. The study should shed some light on the possible involvement of such Co(III) skeleton in inert interactions with biomolecules. The reactivity and speciation of the complex has been found similar to that of the parent cyclen derivative with the presence of mono- and bis-hydroxo-bridged species; at pH < 7.1, all reactivity has been found to be related to the aqua/hydroxo monomeric complexes. Under these pH conditions, the substitution reactions of the aqua/hydroxo ligands by chloride, inorganic phosphate, thymidine, cytidine 5'-monophosphate (5'-CMP), and thymidine-5'-monophosphate (5'-TMP) have been studied at varying conditions; ionic strength has been kept at 1.0 NaClO4 due to the high concentration of 2-(N-morpholino)ethanesulfonic acid (MES) or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) used to ensure buffering. Except for chloride, the process occurs neatly in a one or two step process, showing dissociatively activated substitution mechanisms, having in general large ΔH(⧧), positive ΔS(⧧), and values of ΔV(⧧) close to those corresponding to the liberation of an aqua ligand to the reaction medium. The actuation of noticeable encounter-complex formation equilibrium constants has been found to be the determinant for the reactions with nucleosides and nucleotides, a clear indication of the relevance of hydrogen-bonding interactions in the reactivity of these molecules, even in this highly ionic strength medium. For the substitution of the active aqua/hydroxo ligands with 5'-TMP, the first substitution reaction produces an Nthymine-bound 5'-TMP complex that evolves to a bis-5'-TMP with an Nthymine,Ophosphate-bonding structure. The formation of outer-sphere complexes between the dangling phosphate group of the Nthymine-bound 5'-TMP and the thymine moiety of another entering 5'-TMP has been found to be responsible for this fact, which leaves only the phosphate group for coordination available.

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Section: Resultsmentioning

confidence: 99%

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Martı́nez

Vázquez

2015

Inorg. Chem.

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“…These proteins can be used to achieve both regio- and chemoselective O -acylation on a wide variety of substrates. 29,30 Of particular interest is the ability of many lipases to function in organic solvents, which allows the enzymes to retain their specificity while catalyzing reactions that would not be possible in water. 31 Selective O -acylation of a model peptide containing both serine and lysine residues has been achieved using a lipase isolated from Pseudomonas sp .…”

Section: Chemoselective Transformation Of Hydroxyl Groups In Small Momentioning

confidence: 99%

Chemoselective hydroxyl group transformation: an elusive target

Trader

Carlson

2012

Mol. BioSyst.

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The selective reaction of one functional group in the presence of others is not a trivial task. A noteworthy amount of research has been dedicated to the chemoselective reaction of the hydroxyl moiety. This group is prevalent in many biologically important molecules including natural products and proteins. However, targeting the hydroxyl group is difficult for many reasons including its relatively low nucleophilicity in comparison to other ubiquitous functional groups such as amines and thiols. Additionally, many of the developed chemoselective reactions cannot be used in the presence of water. Despite these complications, chemoselective transformation of the hydroxyl moiety has been utilized in the synthesis of complex natural product derivatives, the reaction of tyrosine residues in proteins, the isolation of natural products and is the mechanism of action of myriad drugs. Here, methods for selective targeting of this group, as well as applications of several devised methods, are described.

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“…10 Glucosyl phosphoramidite was firstly prepared in the presence of pyridinium trifluoroacetate under anhydrous conditions, and then coupled with nucleosides generating the desired compounds. …”

Section: Abstractsmentioning

confidence: 99%

“…(F) Rodriguez and co-workers reported the synthesis of glucosenucleoside conjugates as anti-HIV prodrugs by using 2-cyanoethyl N,N,N′,N′-tetraisopropylphosphorodiamidite as the phosphinylating reagent. 10 Glucosyl phosphoramidite was firstly prepared in the presence of pyridinium trifluoroacetate under anhydrous conditions, and then coupled with nucleosides generating the desired compounds.…”

Section: Introductionmentioning

confidence: 99%

2-Cyanoethyl N,N,N′,N′-Tetraisopropylphosphorodiamidite

Zhang¹

2012

Synlett

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Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

Cited by 16 publications

References 49 publications

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Chemoselective hydroxyl group transformation: an elusive target

2-Cyanoethyl N,N,N′,N′-Tetraisopropylphosphorodiamidite

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Chemoenzymatic Syntheses and Anti-HIV-1 Activity of Glucose−Nucleoside Conjugates as Prodrugs

Cited by 16 publications

References 49 publications

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of CoIII Complexes of Fully Alkylated Cyclen

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of CoIII Complexes of Fully Alkylated Cyclen

Chemoselective hydroxyl group transformation: an elusive target

2-Cyanoethyl N,N,N′,N′-Tetraisopropylphosphorodiamidite

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Product

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Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen

Kinetico-Mechanistic Studies of Nucleoside and Nucleotide Substitution Reactions of Co^III Complexes of Fully Alkylated Cyclen