University of California

Rutgers, The State University of New Jersey

Chiron Corporation

Malin Young

Irwin D Kuntz

Bradford W Gibson

George Lommel Kenyon

Eric W Taylor

Edward Arnold

Gavin D Dollinger

Diana C Roe

Connie M Oshiro

Ning Tang

Andrew Leavitt

Angelika Muscate

Dolan Eargle

Karl Maurer

Judith C Hempel

Margaret Stauber

Todd J Ewing

Allan G Skillman, Jr

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 relates to a novel class of compounds that are potent inhibitors of HIV reverse transcriptase and HIV integrase. In addition to being multienzyme inhibitors, the inventive compounds of the present invention are remarkable in at least two other respects. First, they do not appear to be toxic to cells at typical therapeutic concentrations. Second, they appear to be equally effective against mutant strains of HIV reverse transcriptase commonly found in patients who have developed resistance to current reverse transcriptase inhibitors. Because the inventive compounds show promise in combatting viral resistance and are potent inhibitors of both HIV reverse transcriptase and integrase, they are ideal candidates for use in combination with existing therapies or alone in treating AIDS or HIV infection.

Naphthols useful in antiviral methods

Growing community of inventors

Newark, CA, United States of America

Malin Young