Method of inhibitor design and identification using a 3-D structure of human peptide deformylase
AssigneeSloan-Kettering Institute for Cancer Research
InventorsDavid A. Scheinberg, Sindy Noemi Escobar-Alvarez, Yehuda Goldgur, Yueming Li
Life of this patent
Estimating the term…
Abstract
The present invention provides the three-dimensional structure of human mitochondrial Homo sapiens peptide deformylase (HsPDF) protein, and HsPDF complexed to a binding compound, such as a PDF inhibitor. This crystallographic information will aid in the identification and development of novel binding compounds of HsPDF and other PDF family members which have anti-bacterial, anti-viral, anti-parasitical, anti-inflammatory, and/or anti-cancer activity.
Claims10
A method for the design and identification of a potential binding compound for human peptide deformylase (HsPDF) comprising the steps of:
- (a) generating, on a computer, a three-dimensional structure of HsPDF having the structural coordinates of Tables 1 and/or 2;
- (b) identifying amino acid residues forming an HsPDF active site from the three-dimensional structure of HsPDF from step (a) in order to generate a three-dimensional model of the HsPDF active site, wherein the HsPDF active site comprises amino acids 50CVGLSAPQ57 (SEQ ID NO:10), 112EGCES116 (SEQ ID NO:12), and 156HEMDHL161 (SEQ ID NO:13), and 176TNVYWMKVND185 (SEQ ID NO:8) according to Table 1 and/or 2;
- (c) designing and/or selecting a compound that potentially binds to the HsPDF active site using the three-dimensional model of the HsPDF active site;
- and
- (d) synthesizing and/or choosing the potential binding compound.
A method for the design and identification of a potential binding compound for HsPDF comprising the steps of:
- (a) generating, on a computer, a three-dimensional structure of HsPDF having the structural coordinates of Tables 1 andor 2;
- (b) identifying amino acid residues and a Co2+ cation forming an HsPDF active site from the three-dimensional structure of HsPDF from step (a) in order to generate a three-dimensional model of the HsPDF active site, wherein the HsPDF active site comprises amino acids 50CVGLSAPQ57(SEQ ID NO:10), 112EGCES116 (SEQ ID NO:12), 156HEMDHL161 (SEQ ID NO:13) 176TNVYWMKVND185 (SEQ ID NO:8) , and the cation Co2+ according to Tables 1 and/or 2;
- (c) designing and/or selecting a compound that potentially binds to at least one amino acid in the active site of HsPDF using the three-dimensional model of the HsPDF active site from step (b);
- and
- (d) synthesizing and/or choosing the potential binding compound.
Dependencies are inferred from the claim text.