ABSTRACT
Preparation and spectroscopic properties of novel boron-containing derivatives of anti-HIV agent stavudine are presented, The new compounds, (5'-O-(4,4,5,5-tetramethyl-1,3,2-dioxaboronate)-2'-3'-didehydro-2'-3'-dideoxythymidine and 5'-O-(dihydroxyboronate)-2'-3'-didehydro-2'-3'-dideoxythymidine), were prepared by direct reaction between stavudine and reagents containing BH moieties - pinacolborane and borane-dimethylsulfide complexes, respectively. The boron coordination equilibrium of those compounds was analyzed by water titration monitored by NMR. Results of the DFT calculations and NMR experiments pointed to structural and electronic similarity of tetrahedral boron complexes to phosphate group.
Subject(s)
Anti-HIV Agents/chemical synthesis , Boranes/chemistry , Stavudine/analogs & derivatives , Anti-HIV Agents/chemistry , Magnetic Resonance Spectroscopy , Models, Molecular , Stavudine/chemical synthesis , Stavudine/chemistryABSTRACT
In search of an activity-preserving protein thiophosphorylation method, with thymidylate synthase recombinant protein used as a substrate, potassium thiophosphoramidate and diammonium thiophosphoramidate salts in Tris- and ammonium carbonate based buffer solutions were employed, proving to serve as a non-destructive environment. Using potassium phosphoramidate or diammonium thiophosphoramidate, a series of phosphorylated and thiophosphorylated amino acid derivatives was prepared, helping, together with computational (using density functional theory, DFT) estimation of (31)P NMR chemical shifts, to assign thiophosphorylated protein NMR resonances and prove the presence of thiophosphorylated lysine, serine and histidine moieties. Methods useful for prediction of (31)P NMR chemical shifts of thiophosphorylated amino acid moieties, and thiophosphates in general, are also presented. The preliminary results obtained from trypsin digestion of enzyme shows peak at m/z 1825.805 which is in perfect agreement with the simulated isotopic pattern distributions for monothiophosphate of TVQQQVHLNQDEYK where thiophosphate moiety is attached to histidine (His(26)) or lysine (Lys(33)) side-chain.
Subject(s)
Amino Acids/chemistry , Ions/chemistry , Phosphates/chemistry , Thymidylate Synthase/chemistry , Amides/chemistry , Amino Acid Sequence , Animals , Caenorhabditis elegans/enzymology , Histidine/chemistry , Humans , Lysine/chemistry , Magnetic Resonance Spectroscopy , Phosphoric Acids/chemistry , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Thymidylate Synthase/metabolism , Trypsin/metabolismABSTRACT
Synthesis of 4-hydroxyborauracil and 4-hydroxy-3-methylborauracil, the first boron analogues of uracil, and comparison of their 1H and 13C NMR properties with those of uracil, are presented. The analyses of NMR-monitored boron compound-alcohol and boron compound-amine interactions pointed to the existence of sp3-hybridized, B,B-bis-methoxyborauracils and pyridine-/n-butylamine-borauracils ate-complexes in solution.
Subject(s)
Boron/chemistry , Uracil/analogs & derivatives , Uracil/chemical synthesis , Magnetic Resonance Spectroscopy , Uracil/chemistryABSTRACT
Novel boron compounds, a series of 4-hydroxy-5,6-dihydroborauracil and 4-hydroxy-5,6-dihydroborathymine derivatives containing various substituents at 3-, 5- and 6-positions, is presented. The spectroscopic properties, along with analyses of NMR-controlled boron compound-alcohol and boron compound-amine interactions, proves the existence of sp(3)-hybridized, stable B,B-bis-methoxy-5,6-dihydroborauracils and pyridine-/n-butylamine-5,6-dihydroborauracils ate-complexes in solution.
Subject(s)
Boron Compounds/chemical synthesis , Magnetic Resonance Spectroscopy/methods , Thymine/analogs & derivatives , Uracil/analogs & derivatives , Boron Compounds/chemistryABSTRACT
Novel boron compounds - 5,6-saturated borauracil derivatives (4-bromo-5,6-dihydroborauracil, 4-hydroxy-5,6-dihydroborauracil and 4-methoxy-5,6-dihydroborauracil) are presented along with other boron compounds obtained from N-vinylurea: N-substituted beta-boronic amino acid - 2-{[(dihydroxyborano-amino)(dihydroxyboranooxy)methyl]-amino}ethylboronic acid and substituted methoxy-borane O-[(1-amino-1-N-vinylamino)methyl]dihydroxyboronate.
Subject(s)
Uracil/analogs & derivatives , Magnetic Resonance Spectroscopy , Uracil/chemical synthesis , Uracil/chemistryABSTRACT
During the last few decades microporous and mesoporous materials have been considered for medical use due to biological properties and stability in biological environment. Zeolites have been investigated as drug carriers, and as adjuvants in anticancer therapy, dietetic supplements or antimicrobial agents. This review gives a brief overview of the major aspects of molecular sieves applications in medicine.