Alok K. Upadhyay

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HIV-1 RT is a heterodimeric enzyme, comprising of the p66 and p51 subunits. Earlier, we have shown that the β7-β8 loop of p51 is a key structural element for RT dimerization (Pandey et al., Biochemistry 40: 9505, 2001). Deletion or alanine substitution of four amino acid residues of this loop in the p51 subunit severely impaired DNA binding and catalytic(More)
Lys154 is the only positively charged residue located in the VLPQGWK motif on the beta8-alphaE loop at the junction of the fingers and palm subdomains of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Some of the conserved residues in this motif are critical for RT function, while others have been shown to confer nucleoside drug(More)
Since the discovery and synthesis of a novel DNA mimic, peptide nucleic acid (PNA) in 1991, PNAs have attracted tremendous interest and have shown great promise as potential antisense drugs. They have been used extensively as tools for specific modulation of gene expression by targeting translation or transcription processes. This review discusses the(More)
Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the(More)
Hepatitis C virus (HCV) infection leading to chronic hepatitis is a major factor in the causation of liver cirrhosis, hepatocellular carcinoma, and liver failure. This process may involve the interplay of various host cell factors, as well as the interaction of these factors with viral RNA and proteins. We report a novel strategy using a sequence-specific(More)
The human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a heterodimeric enzyme composed of p66 and p51 subunits. Earlier, we showed that the beta7-beta8 loop of p51 is crucial for polymerase activity of HIV-1 RT as either deletion or Ala substitution of amino acids in the beta7-beta8 loop spanning residues 136-139 in the p51 subunit(More)
Reverse transcriptases from HIV-1 and MuLV respectively prefer Mg2+ and Mn2+ for their polymerase activity, with variable fidelity, on both RNA and DNA templates. The function of the RNase H domain with respect to these parameters is not yet understood. To evaluate this function, two chimeric enzymes were constructed by swapping the RNase H domains between(More)
We have demonstrated that polyamide nucleic acids complementary to the transactivation response (TAR) element of HIV-1 LTR inhibit HIV-1 production when transfected in HIV-1 infected cells. We have further shown that anti-TAR PNA (PNA(TAR)) conjugated with cell-penetrating peptide (CPP) is rapidly taken up by cells and exhibits strong antiviral and(More)
Anti-human immunodeficiency virus-1 (HIV-1) polyamide (peptide) nucleic acids (PNAs) conjugated with cell-penetrating peptides (CPPs) targeted to the viral genome are potent virucidal and antiviral agents. Earlier, we have shown that the anti-HIV-1 PNA(TAR)-penetratin conjugate is rapidly taken up by cells and is nontoxic to mice when administered at repeat(More)
Fingers domain of HIV-1 RT is one of the constituents of the dNTP-binding pocket that is involved in binding of both dNTP and the template-primer. In the ternary complex of HIV-1 RT, two residues Trp-24 and Phe-61 located on the β1 and β3, respectively, are seen interacting with N + 1 to N + 3 nucleotides in the template overhang. We generated(More)