The Natural Products Chemistry Section, LBC, NIDDK has several ongoing projects whose long term aim is to identify and design inhibitors and probes of HIV-1 Envelope-mediated cell fusion. These include the design and development of new gp41-derived peptides and proteins that have dual functions as inhibitors and immunogens, discovery and high resolution structural characterization of new carbohydrate binding proteins that potently inhibit HIV-1 Entry through carbohydrate-mediated interactions with gp120/gp41, discovery of natural product inhibitors of HIV-1 fusion, and structural and mechanistic studies of HIV-1 Envelope - coreceptor interactions.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2008
Total Cost
$507,187
Indirect Cost
City
State
Country
United States
Zip Code
Bewley, Carole A (2008) Illuminating the switch in influenza viruses. Nat Biotechnol 26:60-2
Gustchina, Elena; Louis, John M; Lam, Son N et al. (2007) A monoclonal Fab derived from a human nonimmune phage library reveals a new epitope on gp41 and neutralizes diverse human immunodeficiency virus type 1 strains. J Virol 81:12946-53
Plaza, Alberto; Gustchina, Elena; Baker, Heather L et al. (2007) Mirabamides A-D, depsipeptides from the sponge Siliquariaspongia mirabilis that inhibit HIV-1 fusion. J Nat Prod 70:1753-60
Huang, Chih-Chin; Lam, Son N; Acharya, Priyamvada et al. (2007) Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 317:1930-4
Gustchina, Elena; Louis, John M; Bewley, Carole A et al. (2006) Synergistic inhibition of HIV-1 envelope-mediated membrane fusion by inhibitors targeting the N and C-terminal heptad repeats of gp41. J Mol Biol 364:283-9
Plaza, Alberto; Bewley, Carole A (2006) Largamides A-H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp. J Org Chem 71:6898-907
Mares, Jiri; Muller, Jan U; Skirgailiene, Audrone et al. (2006) A model for cell-surface-exposed carbohydrate moieties suitable for structural studies by NMR spectroscopy. Chembiochem 7:1764-73
Gutierrez-Lugo, Maria-Teresa; Newton, Gerald L; Fahey, Robert C et al. (2006) Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis. Protein Expr Purif 50:128-36
Williams Jr, David C; Lee, Jae Young; Cai, Mengli et al. (2005) Crystal structures of the HIV-1 inhibitory cyanobacterial protein MVL free and bound to Man3GlcNAc2: structural basis for specificity and high-affinity binding to the core pentasaccharide from n-linked oligomannoside. J Biol Chem 280:29269-76
Dimitrov, Antony S; Louis, John M; Bewley, Carole A et al. (2005) Conformational changes in HIV-1 gp41 in the course of HIV-1 envelope glycoprotein-mediated fusion and inactivation. Biochemistry 44:12471-9

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