Compounds and methods for identifying compounds which inhibit a new class of aspartyl proteases
AssigneeTrustees of Dartmouth College
InventorsRonald K. Taylor, Christian F. LaPointe
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Abstract
Compounds and methods for designing and identifying compounds which inhibit TFPP-like aspartyl protease enzymes by targeting the aspartic acid residues of the active site or mimicking peptides corresponding to the region surrounding the substrate's cleavage site are provided. Agents identified as inhibitors of TFPP-like aspartyl proteases such as type 4 prepilin peptidases are expected to be useful as anti-bacterial agents and in inhibiting development of drug resistant strains of bacteria.
Claims11
A method of designing inhibitors of type 4 prepilin peptidase (TFPP)-like aspartyl protease enzymes comprising:
- (a) synthesizing a compound which targets aspartic acid residues of an enzymatic active site of a TFPP-like aspartyl protease enzyme or mimics a region surrounding a cleavage site of a TFPP-like aspartyl protease substrate;
- and
- (b) determining the ability of the synthesized compound to inhibit cleavage activity of the TFPP-like aspartyl protease enzyme.
A method of identifying potential inhibitors of TFPP-like aspartyl protease enzymes comprising:
- (a) selecting a test compound having a structure known to or suspected of targeting aspartic acid residues or mimicking a region surrounding a cleavage site of a TFPP-like aspartyl protease substrate;
- and
- (b) determining the ability of the identified test compound to inhibit cleavage activity of the TFPP-like aspartyl protease enzyme.
A mutant construct of TcpJ wherein an amino acid at position 18, 46, 48, 51, 65, 73, 76, 81, 88, 125, 172, 183, 189, 191, 212, or 213 of SEQ ID NO:4 is mutated.
A nucleic acid sequence encoding a type 4 prepilin peptidase homologue in Staphylococcus aureus comprising SEQ ID NO:2.
Dependencies are inferred from the claim text.