Chiron Corporation

University of California

Eric W Taylor

Kirston E Koths

Robert F Halenbeck

Alice M Wang

Clayton L Casipit

Sung-Hou Kim

Anna Lisa Fear

Jarmila Jancarik

Jayvardhan Pandit

Ralph Yamamoto

Andrew Bohm

Irwin D Kuntz

Bradford W Gibson

Gavin D Dollinger

Malin Young

Connie M Oshiro

Jacqueline A Gibbons

Corine M Dietz

Ning Tang

Judith C Hempel

The present invention provides a fast and efficient method for determining the three-dimensional conformation of a protein. The steps of the method of the invention include: 1) formation of physical distance constraints, e.g., forming intramolecular chemical crosslinks of known size between residues of a protein; 2) enriching the number of the molecules that have intramolecular chemical crosslinks in the reaction pool, e.g., using size separation to remove proteins with intermolecular bonds; 3) exposing the enriched reaction pool to a protease that cuts the protein at specific sites to produce peptide fragments; 4) measuring the size of the peptide fragments to determine linkage sites with a certain spatial relationship in the protein; and 5)interpreting the data produced to determine spatial geometry and protein structure based on the deduced spatial relationship of the linkage sites. The information is preferably analyzed with aid from a computer system, which can be used to generate and/or analyze distance constraints between amino acids.

Method of determining the three-dimensional shape of a macromolecule

The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

Soluble extracellular domain of human M-CSF receptor

A purified glycoprotein complex of over 1200 kD apparent native molecular weight having a sedimentation value of approtely 25S and having the ability to selectively bind human Mac-2 or interfere with PHA activation of lymphocytes, DNA sequences that encode the protein, and expression systems for expressing it, thus providing for medicaments that are useful for treating or diagnosing diseases, including cancer, infectious disease, and diseases of the immune system.

Secreted mac-2-binding glycoprotein

Identification of M-CSF agonists and antagonists

A method for analyzing the ADME/PK properties of a mixture of compounds is (1) perfusing an animal or organ with a perfluorocarbon emulsion blood substitute, (2) administering the mixture of test compounds, (3) withdrawing an aliquot of the perfusate, (4) disrupting the emulsion, and (5) analyzing the aqueous phase of the perfusate for the concentration of test compounds.

ADME analysis of mixtures

A purified glycoprotein complex of over 1200 kD apparent native molecular weight having a sedimentation value of approximately 25S and having the ability to selectively bind human Mac-2 or interfere with PHA activation of lymphocytes, DNA sequences that encode the protein, and expression systems for expressing it, thus providing for medicaments that are useful for treating or diagnosing diseases, including cancer, infectious disease, and diseases of the immune system.

Nucleic acid encoding secreted Mac-2 binding glycoprotein

Crystallization of M-CSF.alpha.

A purified glycoprotein complex of over 1200 kD apparent native molecular weight having a sedimentation value of approximately 25S and having the ability to selectively bind human Mac-2 or interfere with PHA activation of lymphocytes, DNA sequences that encode the protein, and expression systems for expressing it, thus providing for reagents that are useful for treating or diagnosing diseases, including cancer, infectious disease, and diseases of the immune system, and for monitoring the concentration of the glycoprotein in human milk.

Secreted Mac-2-binding glycoprotein

Method for purifying secreted Mac-2-binding glycoprotein

Growing community of inventors

Berkeley, CA, United States of America

Eric W Taylor