__________________________________________________________________________________ <strong>Center</strong> <strong>for</strong> <strong>Advanced</strong> <strong>Biotechnology</strong> <strong>and</strong> <strong>Medicine</strong> Edward Arnold some of the engineered viruses (<strong>and</strong> soon peptides), alone <strong>and</strong> in complex with anti-HIV antibodies. Ultimately we hope to identify three-dimensional correlates of immunogenicity, <strong>and</strong> use this in<strong>for</strong>mation to develop a structural basis <strong>for</strong> design of more effective human vaccines. There is every reason to expect that a structure-based approach to vaccine development will become as important to vaccinology as has structure-based drug design to drug discovery <strong>and</strong> development. In addition to working to develop novel vaccines <strong>and</strong> chemotherapeutic agents, the laboratory aims to gain greater insights into the basic molecular processes of living systems. Other projects currently being pursued in the lab include structural studies of: 1) the human mRNA capping enzyme <strong>and</strong> its associated factors (with Dr. Aaron Shatkin at CABM); 2) the TNF-like cytokine BLyS (B lymphocyte stimulator, with Yuling Li <strong>and</strong> colleagues at Human Genome Sciences); 3) <strong>and</strong> hantavirus proteins (with Dr. Colleen Jonssen at University of New Mexico). The structural group also collaborates with Dr. Gaetano Montelione (CABM) on crystallography of proteins targeted by the Northeast Structural Genomics Consortium. Publications: Sarafianos, S.G., Das, K., Tantillo, C., Clark, A.D. Jr., Ding, J., Whitcomb, J., Boyer, P.L., Hughes, S.H. <strong>and</strong> Arnold, E. (<strong>2001</strong>). Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J. 20: 1449-1461. Boyer, P.L., Sarafianos, S.G., Arnold, E. <strong>and</strong> Hughes, S.H. (<strong>2001</strong>). Selective excision of AZT by drug-resistant human immunodeficiency virus reverse transcriptase. J. Virol. 75:4832-4842. Das, K, Xiong, X., Yang, H., Westl<strong>and</strong>, C.E., Gibbs, C.S., Sarafianos, S.G. <strong>and</strong> Arnold, E. (<strong>2001</strong>). Molecular modeling <strong>and</strong> biochemical characterization reveals the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) <strong>and</strong> emtricitabine (FTC). J. Virol. 75:4771-4779. Hsiou, Y., Ding, J., Das, K., Clark, A.D., Jr., Boyer, P.L., Lewi, P., Janssen, P.A.J., Kleim, J.P. Rösner, M., Hughes, S.H. <strong>and</strong> Arnold, E. (<strong>2001</strong>). The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. J. Mol. Biol. 309:437-445. Tachedjian, G., Orlova, M., Sarafianos, S.G., Arnold, E. <strong>and</strong> Goff, S.P. (<strong>2001</strong>). Nonnucleoside reverse transcriptase inhibitors are chemical inducers of dimerization of the human immunodeficiency type 1 reverse transcriptase. Proc. Natl. Acad. Sci. USA. 98:7188-7193. Boyer, P.L., Gao, H.-Q., Clark, P.K., Sarafianos, S.G., Arnold, E. <strong>and</strong> Hughes, S.H. (<strong>2001</strong>). YADD mutants of human immunodeficiency virus type 1 <strong>and</strong> Moloney murine leukemia virus 28
__________________________________________________________________________________ <strong>Center</strong> <strong>for</strong> <strong>Advanced</strong> <strong>Biotechnology</strong> <strong>and</strong> <strong>Medicine</strong> Edward Arnold reverse transcriptase are resistant to lamivudine triphosphate (3TCTP) in vitro. J. Virol. 75:6321- 6328. Rossmann, M.G. <strong>and</strong> Arnold, E. (<strong>2001</strong>). Editors of "International Tables <strong>for</strong> X-Ray Crystallography, Volume F: Crystallography of Biological Macromolecules.” Kluwer Academic Publishers, Dordrecht, 832 pages. Arnold, E. <strong>and</strong> Rossmann, M.G. (<strong>2001</strong>). Overview of this volume. In "International Tables <strong>for</strong> X-Ray Crystallography, Volume F: Crystallography of Biological Macromolecules," M.G. Rossmann <strong>and</strong> E. Arnold, editors. Kluwer Academic Publishers, Dordrecht, pp. 1-3. Arnold, E. (<strong>2001</strong>). Gazing into the crystal ball: Perspectives <strong>for</strong> the future. In "International Tables <strong>for</strong> X-Ray Crystallography, Volume F: Crystallography of Biological Macromolecules," M.G. Rossmann <strong>and</strong> E. Arnold, editors. Kluwer Academic Publishers, Dordrecht, p. 26. Arnold, E. <strong>and</strong> Rossmann, M.G. (<strong>2001</strong>). Noncrystallographic symmetry averaging of electron density <strong>for</strong> molecular-replacement phase refinement <strong>and</strong> extension. In "International Tables <strong>for</strong> X-Ray Crystallography, Volume F: Crystallography of Biological Macromolecules," M.G. Rossmann <strong>and</strong> E. Arnold, editors. Kluwer Academic Publishers, Dordrecht, pp. 279-292 Ding, J. <strong>and</strong> Arnold, E. (<strong>2001</strong>). Survey of programs <strong>for</strong> crystal structure determination <strong>and</strong> analysis of macromolecules. In "International Tables <strong>for</strong> X-Ray Crystallography, Volume F: Crystallography of Biological Macromolecules," M.G. Rossmann <strong>and</strong> E. Arnold, editors. Kluwer Academic Publishers, Dordrecht, pp. 685-694. Rossmann, M.G. <strong>and</strong> Arnold, E. (<strong>2001</strong>). Patterson <strong>and</strong> molecular replacement techniques. In International Tables <strong>for</strong> Crystallography. Shmueli, U., ed. Vol. B: Reciprocal Space. Kluwer Academic Publishers, Dordrecht, 2 nd edition, pp. 235-263. Ludovici, D.W., Kukla, M.J., Grous, P.G., Krishnan, S., Andries, K., de Béthune, M.-P., Azijn, H., Pauwels, R., De Clercq, E., Arnold, E. <strong>and</strong> Janssen, P.A.J. (<strong>2001</strong>). Evolution of anti-HIV drug c<strong>and</strong>idates. Part 1: From ∝-Anilinophenylacetamide (∝-APA) to imidoyl thiourea (ITU). Bioorg. Med. Chem. Lett. 11:2225-2228. Ludovici, D.W., Kavash, R.W., Kukla, M.J., Ho, C.Y., Ye, H., De Corte, B.L., Andries, K., de Béthune, M.P., Azijn, H., Pauwels, R., Moereels, H.E.L., Heeres, J., Koymans, L.M.H., de Jonge, M.R., Van Aken, K.J.A., Daeyaert, F.F.D., Lewi, P., Das, K., Arnold, E. <strong>and</strong> Janssen, P.A.J. (<strong>2001</strong>). Evolution of Anti-HIV Drug C<strong>and</strong>idates Part 2: Diaryltriazine (DATA) Analogues. Bioorg. Med. Chem. Lett. 11:2229-2234. Ludovici, D.W., De Corte, B.L., Kukla, M.J., Ye, H., Ho, C.Y., Lichtenstein, M.A., Kavash, R.W., Andries, K., de Béthune, M.-P., Azijn, H., Pauwels, R., Lewi, P.J., Heeres, J., Koymans, L., de Jonge, M., Van Aken, K.J.A., Daeyaert, F.F.D., Das, K., Arnold, E. <strong>and</strong> Janssen, P.A.J. 29
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