Schering Corporation

Imiplex LLC

The Dupont Merck Pharmaceutical Company

Columbia University

Dupont Pharmaceuticals Company

Patricia C Weber

Paul Reichert

Nanhua Hugh Yao

Ashit K Ganguly

William Henry Miller

Corey Strickland

William T Windsor

Gregory James Pacofsky

Eugene Cruz Amparo

John Wityak

John J Duncia

F Raymond Salemme

Bruce A Malcolm

Eric William Kaler

S Shane Taremi

Donald W Landry

Joseph B Santella

Vincent Stewart Madison

Zhi Hong

John Matthew Fevig

Francis Raymond Salemme

Tattanahalli L Nagabhushan

Michael H Gelb

Robert A Galemmo, Jr

Shi-Xian Deng

Konstantin Petrukhin

Charles A Lesburg

Matthew M Abelman

Rumin Zhang

Andrew Wasmuth

Shahriar Shane Taremi

Joseph Cacciola

Winifred W Prosise

Kirsten Alison Rinderspacher

Charles W McNemar

Anthony F Mannarino

Andras Varadi

Robert M Knabb

Jennifer Joanne Gesell

Zhen Wu

Mark A Rould

Michael Cable

Joseph Basil Santella, Iii

Philip W Mui

Bruce O Stuart

Rowena F Choudrie

Boglarka Racz

Peter Bernstein

Daniel F Wyss

Dingjiang Liu

The present invention provides a compound having the structure: wherein R, R, R, R, and Rare each independently H, halogen, CF, C-Calkyl, aryl or heteroaryl; X is N or CR, wherein Ris H, OH, or halogen; A is absent or present, and when present is B has the structure: or a pharmaceutically acceptable salt thereof.

Triazolopyrimidines, their preparation and use

A method of assembling a protein nanostructure on a surface including selectively patterning a surface with a fixation site, bringing a protein node into contact with the surface, and allowing the protein node to bond with the fixation site, so that the position and/or orientation of the protein node is constrained, and compositions.

Method of protein nanostructure fabrication

Engineered proteins are used in the assembly of two-dimensional and three-dimensional nanostructure assemblies, based on systematic design and production of protein node structures that can be interconnected, for example, with streptavidin or streptavidin-incorporating struts to produce structures with defined dimensions and geometry. Nanostructure assemblies having utility as functional devices or as resists for the patterning of substrates have architectures including polygons, polyhedra, two-dimensional lattices, and three-dimensional lattices.

Node polypeptides for nanostructure assembly

A streptavidin macromolecular adaptor (SAMA) protein may be used for the controlled assembly of nanostructure building blocks and struts including streptavidin:SAMA complexes.

Streptavidin macromolecular adaptor and complexes thereof

This invention provides fragments of HCV NS3 helicase, and crystalline compositions thereof, based on subdomains of HCV helicase protein. The protein fragments are stable, soluble, and structurally sound. They can be expressed at high levels in conventional expressions systems, such as, to permit efficient, large-scale production for NMR-based screening applications and production of [H,C,N]- and [C,N]-labeled polypeptides for structural NMR studies. Helicase fragments of the present invention are useful in the most advanced NMR techniques available, e.g., NMR-based drug discovery techniques such as SAR-by-NMR, in biological assays to discover inhibitors of HCV NS3 helicase, and to evaluate the mechanism of action and substrates for HCV NS3 helicase. Crystals of the present invention are useful for structure-based drug design studies using x-ray crystallographic techniques.

Hepatitis C virus NS3 helicase subdomain I

Covalent HCV NS4A-NS3 complexes comprising the central hydrophobic domain of native HCV NS4A peptide, a linker, and the HCV NS3 serine protease domain, wherein the hydrophobic domain of native HCV NS4A peptide is tethered by the linker to the amino terminus of the HCV NS3 protease domain.

Single-chain recombinant complexes of hepatitis C virus NS3 protease and NS4A cofactor peptide

Treatment of malaria with farnesyl protein transferase inhibitors

The present invention relates to compositions and crystals of farnesyl protein transferase and farnesyl protein transferase in complex with substrates and inhibitors. Also disclosed are crystallization conditions for these compositions and their use for structural determination of FPT:FPP/FPP analog:peptide/inhibitor complexes.

Crystallizable farnesyl protein transferase compositions, crystals thereby obtained, and methods for use

The present invention relates to crystalline compositions comprising farnesyl protein transferase-like polypeptides in complex with substrates and inhibitors. Also disclosed are crystallization conditions for these compositions and their use for structural determination of FPT:FPP/FPP analog: peptide/inhibitor complexes.

Crystalline farnesyl protein transferase compositions and methods for use

The invention relates to the purification and crystallization of hepatitis C virus (HCV) NS3/NS4A polypeptide complex. Also, crystallization conditions for NS3/NS4A are provided. Further, the atomic coordinates for the NS3/NS4A protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS3/NS4A with substrate(s) or substrate analog(s) or inhibitor complexes are also provided.

Compositions of hepatitis C virus NS3/NS4A complex and methods for crystallizing same

The invention relates to the purification, crystallization of and structure of hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. Also, crystallization conditions for NS5B are provided. Further, the atomic coordinates for the NS5B protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS5B or HCV NS5B in complex with substrates or substrate analogs or inhibitors are also provided.

Compositions of hepatitis C virus NS5B polymerase and methods for crystallizing same

This invention relates to pharmaceutical composition comprising a lipophilic oligosaccharide antibiotic in a substantially monomeric form.

Monomeric lipophilic oligosaccharide antibiotic compositions

This invention relates to electrophilic dipeptide analogs conjugated to an N,N-disubstituted .alpha.-amino acid as inhibitors of trypsin-like serine protease enzymes.

Electrophilic peptide analogs as inhibitors of trypsin-like enzymes

An inhibitor of the HCV NS3 protease. The inhibitor is a subsequence of a substrate of the NS3 protease or a subsequence of the NS4A cofactor. Another inhibitor of the present invention contains a subsequence of a substrate linked to a subsequences of the NS4A cofactor. In another embodiment the inhibitor is a bivalent inhibitor comprised of a subsequence, a mutated subsequence or a mutated full-length of a substrate of the NS3 protease linked to a subsequence, a mutated subsequence or a mutated full-length suquence of the HCV NS4A cofactor.

Synthetic inhibitors of hepatitis C virus NS3 protease

Growing community of inventors

Yardley, PA, United States of America

Patricia C Weber