Abbas Raza

Design and synthesis of sulfoximine based inhibitors for HIV-1 protease.

A new class of potent sulfoximine inhibitors for HIV-1 protease has been designed and synthesized. Substitution of the sulfoximine moiety into different parent compounds yields different inhibition effects. While our previously studied sulfoximine-based inhibitors display potency of 2.5 nM (IC(50)) against HIV-1 protease, introduction of the sulfoximine moiety into the asymmetric Indinavir yielded only micromolar inhibition. Docking studies showed structural variations in their modes of binding which explains this unexpected observation. The implication of these observations in the development of other sulfoximine inhibitors is discussed.

Synthesis of unusual amino acids: N-(tert-butoxycarbonyl)-l-vinyl glycine and N-(tert-butoxycarbonyl)-l-homophenylalanine ☆

The synthesis of the unusual amino acids N-(tert-butoxycarbonyl)-L-vinyl glycine and N-(tert-butoxycarbonyl)-L-homophenylalanine starting from commercially available D-xylose via an alkylative fragmentation method is described.

One Pot Synthesis of Acetylated Homoallyl Alcohols

Abstract An efficient one pot procedure for the preparation of acetylated homoallyl alcohols mediated by TaCl5 is described.

Photoprotection of DNA (in vitro) by acyclothymidine dinucleosides

Excessive exposure to sunlight is primarily implicated in ultraviolet (UV) induced skin cancers worldwide. Direct absorption of UV radiation by DNA leads to the formation of cyclobutane pyrimidine dimers (CPDs) resulting in DNA damage. The molecular mechanisms involved in the mutagenicity of CPDs are well established. Photoprotection of the skin from the detrimental effects of UV is essential in preventing skin damage. A variety of formulations, which essentially contain UV filters have been used as photoprotective agents of the skin. These comprise aromatic and inorganic molecules, whose mechanism of action involves either absorption, reflection, or scattering of UV radiation. However, the downstream photoproducts of some of these molecules have undesirable characteristics which compromise their utility. A biomimetic approach involving structural analogs of nucleic acids can help overcome these limitations. Herein, we show the photoprotective action of acyclothymidine dinucleosides on both plasmid and cellular DNA.

Dehydroascorbic Acid Adducts of Guanosine Residues: Possible Biological Implications

Dehydroascorbic acid (DHA), the oxidation product of vitamin C (ascorbic acid, AA) has many important biological functions beyond the AA–DHA cycle. This report identifies a new and novel conjugate of DHA with guanosine. The spectroscopic and structural data reveal the formation of a new five-membered cyclic structure that is confirmed by X-ray crystallography. DHA inhibition of protein synthesis was examined by using human lysate and rabbit reticulocyte DNAand RNAdependent systems. These findings suggest that in addition to being an antioxidant, AA in its oxidized form can alter DNA or RNA function by direct binding to guanosine. The role of vitamin C in the prevention and treatment of the common cold has been great scientific debate for at least six decades. 2] The general interest in this subject was stimulated originally by the vigorous advocacy of Nobel laureate Linus Pauling during the 1970s and continues to be high. The use of AA to prevent scurvy was first discovered in the 18th century and is now common knowledge. The present-day literature provides many examples of the antitumor and antiviral effects of the vitamin and its metabolic products, DHA and 2,3diketogulonic acid. 9] For the most part, these effects have been attributed to the antioxidant properties of AA, but the mechanistic evidence for the antitumor and antiviral effects of this vitamin has not been well established, and AA’s exact role is still unknown. DHA, 13] an oxidation product of AA (Figure 1 A) is the principal form for cellular uptake through the facilitative glucose transporters. 15] DHA can be present in high concentrations in many tissues and physiological fluids, especially during diseases and aging processes. 17] However, little is known about the reaction of DHA with amino acids, or proteins, although it is proposed that such interactions are responsible for browning pigments. Recent studies suggest that some properties of AA and DHA involve either free-radical formation or inhibition of certain kinase activities. 22] Although, the adducts of certain 1,2-dicarbonyl compounds with guanines are known, the binding of DHA with guanosine has never been reported. AA, a naturally occurring compound is an essential nutrient in the human body; DHA being the main transportable form of vitamin C has prompted us to investigate its binding interactions with guanosine residues. In this report, we propose an additional and more direct mechanism for the action of DHA on biological systems, namely the formation of an adduct between DHA and guanosine. The absorption spectra of DHA and G mixtures revealed adduct formation through wavelength shifts (220–300 nm; Figure 1 B). The shoulder occurring between wavelengths 270 and 280 nm diminished with time, as the maximum at 257 nm in-

Topical Acyclothymidine Dinucleosides (aTds) Promote non-UV Mediated Endogenous Defense Mechanisms in Guinea Pig Skin

TO THE EDITOR According to Lee’s comments and recommendations from a statistical point of view, we recalculated P-values of all the figures except Figures 4, 5c, and 6c. Wilcoxon rank-sum (Mann–Whitney) test and Kruskal–Wallis equality-ofpopulations rank test with a Bonferroni correction were performed. All data showed statistically significant difference (P-values o0.05). Therefore, we concluded that the interaction between natural killer T cells and dendritic cells is important in the sensitization phase of contact hypersensitivity.