Methods for identifying and using MarR family polypeptide binding compounds
AssigneeParatek Pharmaceuticals, Inc.
InventorsMichael N. Alekshun, Stuart B. Levy, Brent L. Podlogar, Roger Frechette
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Abstract
Methods for identifying MarR family inhibiting compounds are described. The methods include the use of computer aided rational based drug design programs and three dimensional structures of MarR family polypeptides.
Claims47
A method of identifying a MarR family modulating compound comprising:
- selecting a candidate MarR family modulating compound by performing rational drug design with the set of atomic coordinates in FIG. 1 or 2, such that a MarR modulating compound is identified.
A method of identifying a MarR family modulating compound comprising:
- determining the structure of a MarR family polypeptide using the structure of MarR, such that a MarR family modulating compound is identified.
A method of identifying a MarR modulating compound comprising:
- obtaining a set of atomic coordinates defining the three-dimensional structure of MarR, wherein MarR has the peptide sequence given in SEQ ID NO. 1;
- selecting a candidate MarR modulating compound by performing rational drug design with said three dimensional structure of MarR;
- contacting said candidate MarR modulating compound with MarR;
- measuring the ability of the candidate MarR modulating compound to modulate the activity of MarR, thus identifying a MarR modulating compound.
A MarR modulating compound of the formula(I):
- X-Y-Z (I)
- wherein
- X is an interacting moiety;
- Y is a hydrophobic moiety;
- and
- Z is a polar moiety.
A method for inhibiting expression of MarA, comprising contacting MarR with a MarR modulating compound, wherein said MarR modulating compound is of the formula(I):
- X-Y-Z (I)
- wherein
- X is an interacting moiety;
- Y is a hydrophobic moiety;
- and
- Z is a polar moiety.
A method for decreasing multidrug resistance in a microbe comprising contacting the microbe with a MarR modulating compound, such that said multidrug resistance of the microbe is decreased, wherein said MarR modulating compound is of the formula(I):
- X-Y-Z (I)
- wherein
- X is an interacting moiety;
- Y is a hydrophobic moiety;
- and
- Z is a polar moiety.
Dependencies are inferred from the claim text.