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AssigneeThe Regents of the University of California
InventorsCorey S. Goodman, Thomas Kidd, Katja Brose, Marc Tessier-Lavigne
Estimating the term…
Disclosed are methods and compositions for identifying agents which modulate the interaction of Robo and a Robo ligand and for modulating the interaction of Robo and a Robo ligand. The methods for identifying Robo:ligand modulators find particular application in commercial drug screens. These methods generally comprise (1) combining a Robo polypeptide, a Slit polypeptide and a candidate agent under conditions whereby, but for the presence of the agent, the Robo and Slit polypeptides engage in a first interaction, and (2) determining a second interaction of the Robo and Slit polypeptides in the presence of the agent, wherein a difference between the first and second interactions indicates that the aget modulates the interaction of the Robo and Slit polypeptides. The subject methods of modulating the interaction of Robo and a Robo ligand involve combining a Robo polypeptide, a Slit polypeptide and a modulator under conditions whereby, but for the presence of the modulator, the Robo and Slit polypeptides engage in a first interaction, whereby the Robo and Slit polypeptides engage in a second interaction different from the first interaction. In a particular embodiment, the modulator is dominant negative form of the Robo or Slit polypeptide.
A recombinant polynucleotide comprising a coding sequence encoding a polypeptide comprising at least one sequence selected from the group consisting of SEQ ID NOS:2-6, 8 and 10-14, or a subsequence thereof having at least 16 consecutive amino acid residues thereof and comprising one or more unboxed amino acid residues of the corresponding sequence in at least one table selected from the group consisting of Table 1 and Table 2, said coding sequence flanked by fewer than 500 bp of native flanking sequence.
A recombinant polynucleotide comprising a coding sequence encoding a polypeptide comprising at least one sequence selected from the group consisting of SEQ ID NOS:2-6 and 8-14.
A recombinant polynucleotide comprising a coding sequence encoding a polypeptide comprising at least one sequence selected from the group consisting of SEQ ID NOS:2-6 and 10-14, or a subsequence thereof having at least 16 consecutive amino acid residues thereof and comprising one or more unboxed amino acid residues of the corresponding sequence in at least one table selected from the group consisting of Table 1 and Table 2, said coding sequence flanked by fewer than 500 bp of native flanking sequence.
A recombinant polynucleotide comprising a strand of SEQ ID NO:01, or a fragment thereof having at least 24 consecutive nucleotides thereof, and sufficient to specifically hybridize under stringent conditions with a polynucleotide having the sequence defined by the corresponding opposite strand of SEQ ID NO:01, said strand or fragment thereof flanked by fewer than 500 bp of native flanking sequence, said stringent conditions consisting of a hybridization buffer of 30% formamide in 5× SSPE (0.18 MNaCl, 0.01M NaPO4, pH7.7, 0.001M EDTA) buffer at a temperature of 42° C. and a wash buffer of 0.2× SSPE at 42° C., and, said fragment comprising at least one sequence selected from the group consisting of:
Dependencies are inferred from the claim text.