ABSTRACT
New homo and heterodimers of ddI, d4T and AZT with (5-5) thiolcarbonate-carbamate linkages have been prepared with the aim of testing them against wild type and NNRTI resistant HIV mutants. The prepared dimers showed a low activity in comparison to the parent drug.
Subject(s)
Anti-HIV Agents/pharmacology , Antiviral Agents/chemistry , Carbamates/chemistry , Didanosine/chemistry , HIV/metabolism , Stavudine/chemistry , Sulfhydryl Compounds/chemistry , Zidovudine/chemistry , Antiviral Agents/pharmacology , Dimerization , HIV/genetics , HIV Infections/drug therapy , Models, Chemical , Molecular Conformation , MutationABSTRACT
Several D-ribonucleosides are prepared from 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranoside and trimethylsilylated nucleobases under mild conditions by using natural phosphate doped with KI as catalyst.
Subject(s)
Molecular Biology/methods , Phosphates/chemistry , Alkylation , Catalysis , Chromatography , Glycosides/chemistry , Glycosylation , Hydrocarbons/chemistry , Indicators and Reagents/chemistry , Methane/analogs & derivatives , Methane/chemistry , Models, Chemical , Nucleosides/chemistry , Potassium Iodide/chemistryABSTRACT
Homo- and heterodimers of AZT and d4T, possessing carbonate and carbamate linkers, have been synthesized with the aim to enhance the antiviral activity of their components. Homo- and heterodimer carbamates showed weak anti-HIV activity. On the other hand, dinucleoside carbonates showed marked antiviral activity.
Subject(s)
Anti-HIV Agents/chemical synthesis , Fungal Proteins/chemistry , Lipase/chemistry , Stavudine/chemical synthesis , Zidovudine/chemical synthesis , Anti-HIV Agents/pharmacology , Cell Line , Dimerization , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-2/drug effects , Humans , Stavudine/pharmacology , Virus Replication/drug effects , Zidovudine/pharmacologyABSTRACT
Doped natural phosphate is used as acidic or basic catalyst in nucleoside and acyclonucleoside synthesis. Some examples are given.
Subject(s)
Nucleosides/chemical synthesis , Phosphates/chemistry , Biological Factors , Catalysis , Kinetics , Mining , Morocco , StereoisomerismABSTRACT
A series of new homo and heterodimers of ddI has been synthesized. A glutarate diester spacer was used to covalently couple ddI onto ddI, AZT or d4T.
Subject(s)
Didanosine/analogs & derivatives , Didanosine/chemistry , Anti-HIV Agents/chemistry , Didanosine/chemical synthesis , Dimerization , Esters , Indicators and Reagents , Molecular Conformation , Stavudine/chemistry , Zidovudine/chemistryABSTRACT
Potassium fluoride doped natural phosphate, inexpensive and environmentally friendly catalyst, is shown to be an efficient basic catalyst for the N1/N9 alkylation of different nucleobases as synthons for PNAs.
Subject(s)
Peptide Nucleic Acids/chemical synthesis , Alkylation , Catalysis , Fluorides/chemistry , Heterocyclic Compounds/chemistry , Magnetic Resonance Spectroscopy , Models, Chemical , Phosphates/chemistry , Potassium Compounds/chemistryABSTRACT
The dependence of the proton spin-lattice relaxation rate, and of the enthalpy and temperature of denaturation on water content, were studied by nmr and differential scanning calorimetry (DSC) in native and denatured collagen. Collagen was first heated at four different temperatures ranging from 40 to 70 degrees C. The percentage of denatured collagen induced by these preheating treatments was determined from DSC measurements. The DSC results are discussed in terms of heat-induced structural changes. A two-exponential behavior for the spin-lattice relaxation was observed with the appearance of denatured collagen. This was attributed to the presence of a noncollagen protein fraction. The variations in the different longitudinal relaxation rates as a function of the moisture content and of the denatured collagen percentage are described within the multiphase water proton exchange model. This study highlights the complementarity of the information obtained from the two analytical tools used.
Subject(s)
Collagen/chemistry , Water/chemistry , Animals , Calorimetry, Differential Scanning , Cattle , Hot Temperature , Magnetic Resonance Spectroscopy , Protein Denaturation , ThermodynamicsABSTRACT
Alkenyl acyclonucleosides derivatives of 5-halogenouracil have been synthesized via Michael addition reaction. These compounds were treated by allylbromide, propargylbromide or ethylbromoacetate to give the corresponding N-1,N-3-disubstituted 5-halogenouracil.
Subject(s)
Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Nucleosides/chemical synthesis , Nucleosides/pharmacology , Uracil/chemistry , Antineoplastic Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Magnetic Resonance SpectroscopyABSTRACT
A proton magnetic resonance study of different cross-linked collagens was performed as a function of water content and temperature. Collagens from three connective tissues (calf, steer, and cow) were chosen according to the different number of nonreducible multivalent cross-links, which increases during the life of animal. Samples were hydrated under five well-defined water activities (Aw) ranging from 0.44 to 0.85. The transverse and cross-relaxation times of water protons were studied as a function of temperature from -20 up to 100 degrees C. From the temperature dependence of relaxation rates, the dynamics of water molecules can be described according to different processes: exchange of protons at the higher temperatures and dipole-dipole interactions that prevail at the lower temperatures. The exchange processes are analyzed as a function of the residence lifetime of water molecules at the protein interface and of the transfer of spin energy from water protons to macromolecule protons. The proton dipole-dipole interactions are related to the relaxation parameters of protein and water protons. All the relaxation parameters showed specific behavior for the 0.44 water activity for every tissue. The collagen tissue from calf also showed distinct behavior in comparison with other tissues.
