The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Feb. 22, 2000
Filed:
Jul. 31, 1997
Igor L Shamovsky, Kingston, CA;
Gregory M Ross, Kingston, CA;
Richard J Riopelle, Kingston, CA;
Donald F Weaver, Kingston, CA;
Queen's University at Kingston, Kingston, CA;
Abstract
The present invention relates to computational methods for identifying the bioactive conformations of peptide domains, in particular the geometries of complexes of neurotrophins and neurotrophin receptors, and the geometries of neurotrophin receptors and ligands. The invention includes a method for identifying and theoretically modelling a receptor binding site for neurotrophins, such as NGF, BDNF, NT-3 and NT4/5, of the common neurotrophin receptor p75.sup.NTR. The principal residues of the p75.sup.NTR binding site are Asp.sup.47p, Lys.sup.56p, Asp.sup.75p, Asp.sup.76p, Asp.sup.88p and Glu.sup.88p of the second and third cysteine-rich domains. These residues interact with residues of variable loop regions I and V and other neighboring residues of each of the neurotrophins. The invention provides a method of designing a ligand for binding with common neurotrophin receptor p75.sup.NTR including computationally evolving a ligand having effective moieties located relative to each other in the ligand so that the moieties bind to at least two of p75.sup.NTR binding loop 2A including region Cys.sup.39p to Cys.sup.58p, p75.sup.NTR binding loop 2B including region Cys.sup.58p to Cys.sup.78p, and p75.sup.NTR binding loop 3A including region Cys.sup.79p to Cys.sup.94p. The invention further provides a method of identifying such a ligand encoded in a data base containing molecules coded for spatial occupancy, relative atomic position, bond type and/or charge. The designed or identified ligand may be an agonist or antagonist of p75.sup.NTR.