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
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
Plaza, Alberto; Bifulco, Giuseppe; Keffer, Jessica L et al. (2009) Celebesides A-C and theopapuamides B-D, depsipeptides from an Indonesian sponge that inhibit HIV-1 entry. J Org Chem 74:504-12
Gustchina, Elena; Bewley, Carole A; Clore, G Marius (2008) Sequestering of the prehairpin intermediate of gp41 by peptide N36Mut(e,g) potentiates the human immunodeficiency virus type 1 neutralizing activity of monoclonal antibodies directed against the N-terminal helical repeat of gp41. J Virol 82:10032-41
Lam, Son N; Acharya, Priyamvada; Wyatt, Richard et al. (2008) Tyrosine-sulfate isosteres of CCR5 N-terminus as tools for studying HIV-1 entry. Bioorg Med Chem 16:10113-20
Nelson, Josh D; Kinkead, Heather; Brunel, Florence M et al. (2008) Antibody elicited against the gp41 N-heptad repeat (NHR) coiled-coil can neutralize HIV-1 with modest potency but non-neutralizing antibodies also bind to NHR mimetics. Virology 377:170-83