Isoprenoid-dependent ras anchorage (idra) proteins
OwnerYoel Kloog, Roni Haklai +3inventors
InventorsYoel Kloog, Roni Haklai, Ariella Paz, Galit El Ad-Sfadia, Eyal Ballan
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Abstract
Disclosed is the identity of various Ras cell membrane anchor proteins. Also disclosed are methods for identifying other anchor proteins that bind isoforms of Ras, methods of identifying drug candidates that inhibit aberrant Ras activity and methods of determining therapeutic dosages of the drugs. Further disclosed are methods for disrupting aberrant Ras activity in vivo.
Claims38
A method for identifying a cell membrane anchor protein that binds a Ras protein, comprising:
- preparing a first reaction mixture comprising the Ras protein, cell membranes or fragments thereof, and a Ras antagonist, and a second reaction mixture comprising the Ras protein and cell membranes or fragments thereof but not the Ras antagonist;
- adding a cross-linking agent to the first and second reaction mixtures whereby cross-linked complexes between the Ras protein and other proteins are produced;
- separating each of the cross-linked complexes individually;
- identifying a complex formed in said second reaction mixture that is disrupted by the Ras antagonist present in said first reaction mixture;
- separating thus-identified complex from other complexes;
- and
- separating the Ras protein from the other protein in the separated complex.
A method for identifying drug candidates that inhibit aberrant Ras activity, comprising:
- preparing a reaction mixture containing a Ras protein, an anchor protein that binds the Ras protein and the drug candidate;
- and
- determining effect of the drug candidate on interaction between the Ras protein and the anchor protein.
A method disrupting aberrant Ras activity in vivo, comprising infusing into a patient exhibiting such aberrant Ras activity, a compound comprising an oligonucleotide molecule that binds mRNA of a Ras anchor protein and inhibits expression of the Ras anchor protein.
A method of determining efficacious dosages of a Ras antagonist that disrupts Ras-anchor protein binding, comprising:
- contacting cells with the antagonist in vivo or in vitro;
- collecting the cells following said contacting;
- isolating cell membranes from the collected cells;
- measuring decrease in anchor protein concentration per unit of cell membrane protein;
- and
- correlating the decrease with dosage of the Ras antagonist.
An antisense compound that specifically binds a nucleic acid encoding galectin-1, galectin-3, galectin-7 or galectin-8, and which and which causes degradation of the nucleic acid.
Dependencies are inferred from the claim text.