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
14
Fiscal Year
2013
Total Cost
$794,394
Indirect Cost
City
State
Country
Zip Code
Dogo-Isonagie, Cajetan; Lee, Su-Lin; Lohith, Katheryn et al. (2016) Design and synthesis of small molecule-sulfotyrosine mimetics that inhibit HIV-1 entry. Bioorg Med Chem 24:1718-28
Mason, Rosemarie D; Welles, Hugh C; Adams, Cameron et al. (2016) Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog 12:e1005537
Stewart-Jones, Guillaume B E; Soto, Cinque; Lemmin, Thomas et al. (2016) Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell 165:813-26
Mason, Rosemarie D; Welles, Hugh C; Adams, Cameron et al. (2016) Correction: Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability. PLoS Pathog 12:e1005674
Acharya, Priyamvada; Lusvarghi, Sabrina; Bewley, Carole A et al. (2015) HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets 19:765-83
Lusvarghi, Sabrina; Ghirlando, Rodolfo; Wong, Chi-Huey et al. (2015) Glycopeptide mimetics recapitulate high-mannose-type oligosaccharide binding and function. Angew Chem Int Ed Engl 54:5603-8
Sastry, Mallika; Bewley, Carole A; Kwong, Peter D (2015) Effective isotope labeling of proteins in a mammalian expression system. Methods Enzymol 565:289-307
Louis, John M; Aniana, Annie; Lohith, Katheryn et al. (2014) Binding of HIV-1 gp41-Directed Neutralizing and Non-Neutralizing Fragment Antibody Binding Domain (Fab) and Single Chain Variable Fragment (ScFv) Antibodies to the Ectodomain of gp41 in the Pre-Hairpin and Six-Helix Bundle Conformations. PLoS One 9:e104683
Pancera, Marie; Shahzad-Ul-Hussan, Syed; Doria-Rose, Nicole A et al. (2013) Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat Struct Mol Biol 20:804-13
Bewley, Carole A; Shahzad-ul-Hussan, Syed (2013) Characterizing carbohydrate-protein interactions by nuclear magnetic resonance spectroscopy. Biopolymers 99:796-806

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