Whitehead Institute for Biomedical Research

Merck + Co., Inc.

Medimmune Limited

Istitute Di Ricerche Di Biologia Molecolare P. Angeletti S.p.a.

Peter S Kim

David C Chan

Debra Muir Eckert

Michael J Root

Min Lu

Vladimir N Malashkevich

James M Berger

Deborah Fass

Michael S Kay

Tara R Suntoke

Peter A Carr

Elisabetta Bianchi

Michael D Miller

John W Shiver

Daria Hazuda

Romas Geleziunas

Simon N Lennard

Antonius Nicolass Schumacher

Vladimir Malashkevich

Five-Helix protein, which comprises the three N-helices and at least two, but not three, of the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, such as amino acid residue linkers, is disclosed. Six-Helix protein, which includes the three N-helices and the three C-helices of the trimer-of-hairpin structure of HIV gp41, separated by linkers, is also disclosed.

Five-helix protein

Inhibitors of HIV membrane fusion and a method of identifying drugs or agents which inhibit binding of the N-helix coiled-coil and the C helix of HIV gp41 envelope protein.

Inhibitors of HIV membrane fusion

Described herein are chimeric peptides comprising a soluble trimeric coiled-coil and all or a portion of the N-peptide region of HIV gp41. These molecules are stable, trimeric coiled-coils that inhibit HIV entry into cells, such as human cells. Such peptides can be further assessed to demonstrate their ability to serve as potent anti-HIV therapeutic molecules and thus, as therapeutic molecules or drugs.

Soluble chimeric peptide inhibitors of HIV entry comprising an IZ trimeric coiled-coil peptide and HIV gp41 N-helix coiled-coil peptide

Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as Vand Vchains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines.

Human antibodies interacting with HIV gp41

Five-Helix protein

Described are the crystal structure of the &#x3b1;-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

Core structure of gp41 from the HIV envelope glycoprotein

Peptide inhibitors of HIV entry

Described are the crystal structure of the &agr;-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

Described are the crystal structure of the .alpha.-helical domain of the gp41 component of HIV-1 envelope glycoprotein which represents the core of fusion-active gp41, methods of identifying and designing drugs which inhibit gp41 function and drugs which do so.

A method of identifying macromolecules (peptides, oligonucleotides, sugars and macromolecular complexes, such as RNA-protein complexes, protein-lipid complexes), which are not of the natural handedness (not of the chirality as they occur in nature or as a wild type molecule) and which are ligands for other chiral macromolecules.

Growing community of inventors

Lexington, MA, United States of America

Peter S Kim