Massachusetts Institute of Technology

Other

Tufts University

Wellesley College

New England Medical Center Hospitals. Inc.

M.i.t.

University of Montreal

Yeda Research and Develpment & Co. Ltd

Arizona Board of Regents, a Body Corporate

Ribozyme Pharmaceuticals, Incorporated

New England Medical Center

Alexander Rich

Shuguang Zhang

Charles A Dinarello

Andrew C Webb

Philip E Auron

Curtis A Lockshin

Todd Holmes

Nassim Usman

Robert J Cedergren

Sheldon M Wolff

Jean-Pierre Perreault

Jing-Hua Yang

Lee Gehrke

Karolina Corin

Lanny J Rosenwasser

C Michael DiPersio

Lotta T Tegler

George M Whitesides

Lin Yan

Marian Gorecki

Meir Wilchek

Bertram L Jacobs

Alan Herbert

Sheldon M Wolff, Deceased

Clemenceau T Acquaye

Lotta Tolstoy Tegler

Alfred E Nordheim

The present invention is directed to a method of preparing a water-soluble variant of a G-protein coupled receptor (GPCR), the method comprising replacing residues leucine (L), isoleucine (I), valine (V), and phenylalanine (F) in hydrophilic surface &#x3b1;-helical positions b, c, and f but not positions a, d, e, and g within the-transmembrane &#x3b1;-helical domain of the GPCR with glutamine (Q), threonine (T), threonine (T), and tyrosine (Y), respectively.

Water soluble membrane proteins and methods for the preparation and use thereof

The present invention is directed to water-soluble membrane proteins, methods for the preparation thereof and methods of use thereof.

Described herein is the self-assembly of amphiphilic peptides, i.e., peptides with alternating hydrophobic and hydrophilic residues, into macroscopic membranes. The membrane-forming peptides are greater than 12 amino acids in length, and preferably at least 16 amino acids, are complementary and are structurally compatible. Specifically, two peptides, (AEAEAKAK)(ARARADAD), were shown to self-assemble into macroscopic membranes. Conditions under which the peptides self-assemble into macroscopic membranes and methods for producing the membranes are also described. The macroscopic membranes have several interesting properties: they are stable in aqueous solution, serum, and ethanol, are highly resistant to heat, alkaline and acidic pH, chemical denaturants, and proteolytic digestion, and are non-cytotoxic. The membranes are potentially useful in biomaterial applications such as slow-diffusion drug delivery systems, artificial skin, and separation matrices, and as experimental models for Alzheimer's disease and scrapie infection. The sequence of the peptide, EAK16, was derived from a putative Z-DNA binding protein from yeast, called zuotin. The cloning and characterization of the ZUO1 gene are also described.

Stable macroscopic membranes formed by self-assembly of amphiphilic peptides and uses therefor

Nucleozymes containing ribonucleotides and deoxyribonucleotides or nucleic acid analogues are described herein. The nucleozymes have catalytic activity and are significantly more resistant to degradation than their all-RNA ribozyme counterparts. Also described are methods for preparing the nucleozymes along with methods of using nucleozymes, e.g., as therapeutic agents.

Nucleozymes

The present invention relates to methods of detecting or identifying inhibitors of a Z-DNA binding ligand to Z-DNA, methods of inhibiting the pathogenicity of an infectious agent, antiviral therapies, and compounds that inhibit complex formation between a Z-DNA binding ligand and Z-DNA.

Method of inhibiting pathogenicity of infectious agents

Described herein is the self-assembly of amphiphilic peptides, i.e., peptides with alternating hydrophobic and hydrophilic residues, into macroscopic membranes. The membrane-forming peptides are greater than 12 amino acids in length, and preferably at least 16 amino acids, are complementary and are structurally compatible. Specifically, two peptides, (AEAEAKAK) (ARARADAD) , were shown to self-assemble into macroscopic membranes. Conditions under which the peptides self-assemble into macroscopic membranes and methods for producing the membranes are also described. The macroscopic membranes have several interesting properties: they are stable in aqueous solution, serum, and ethanol, are highly resistant to heat, alkaline and acidic pH, chemical denaturants, and proteolytic digestion, and are non-cytotoxic. The membranes are potentially useful in biomaterial applications such as slow-diffusion drug delivery systems, artificial skin, and separation matrices, and as experimental models for Alzheimer's disease and scrapie infection. The sequence of the peptide, EAK16, was derived from a putative Z-DNA binding protein from yeast, called zuotin. The cloning and characterization of the ZUO1 gene are also described.

This invention describes self assembled monolayers (SAMs) manufactured by imprinting reactive peptides onto solid supports. The invention further relates to methods of preparing and using these improved SAMs.

Self-assembling peptide surfaces for cell patterning and interactions

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells. The subject invention further concerns antibodies that are immunoreactive with human IL-1.beta. proteins.

Biologically active fragments of IL-1.beta.

The subject invention concerns a nucleic acid comprising a nucleotide sequence encoding human interleukin-1 (IL-1), and fragments thereof, and the polypeptides and peptides obtained. Specifically, the subject invention comprises the cloning of a cDNA synthesized by reverse transcription of poly(A)RNA isolated from adherent human monocytes stimulated with bacterial endotoxin. Human IL-1 is useful to induce the production of IL-2 by activated T-cells; it also acts on B-cells and NK-cells.

Recombinant DNA which codes for interleukin-1

Described herein is the self-assembly of amphiphilic peptides, i.e., peptides with alternating hydrophobic and hydrophilic residues, into macroscopic membranes. The membrane-forming peptides are greater than 12 amino acids in length, and preferably at least 16 amino acids, are complementary and are structurally compatible. Specifically, two peptides, (AEAEAKAK).sub.2 (ARARADAD).sub.2, were shown to self-assemble into macroscopic membranes. Conditions under which the peptides self-assemble into macroscopic membranes and methods for producing the membranes are also described. The macroscopic membranes have several interesting properties: they are stable in aqueous solution, serum, and ethanol, are highly resistant to heat, alkaline and acidic pH, chemical denaturants, and proteolytic digestion, and are non-cytotoxic. The membranes are potentially useful in biomaterial applications such as slow-diffusion drug delivery systems, artificial skin, and separation matrices, and as experimental models for Alzheimer's disease and scrapie infection. The sequence of the peptide, EAK16, was derived from a putative Z-DNA binding protein from yeast, called zuotin. The cloning and characterization of the ZUO1 gene are also described.

Stable macroscopic membranes formed by self-assembly of amphiphilic

Disclosed is the isolation of a 140,000 kDa protein which binds with high affinity to Z-DNA. Z-DNA is defined herein as a non-B-DNA conformer which is stabilized by negative supercoiling. The isolated protein also has a binding site for double-stranded RNA (dsRNA). Peptide sequences from this protein show similarity to double-stranded RNA adenosine deaminase (dsrad), an enzyme which deaminates adenosine in dsRNA to form inosine. Assays for this enzyme confirm that dsrad activity and Z-DNA binding are properties of the same molecule. The coupling of these two activities in a single molecule indicate a novel mechanism of gene regulation which is in part dependent on DNA topology.

Z-DNA binding protein and applications

Growing community of inventors

Cambridge, MA, United States of America

Alexander Rich