Title:
A METHOD FOR HIGH THROUGHPUT THERMODYNAMIC SCREENING OF LIGANDS
Document Type and Number:
WIPO Patent Application WO2001040758
Kind Code:
A3
Abstract:
The present invention provides a method of rapidly screening ligands on the basis of their binding affinity and binding enthalpy by carrying out binding assays at a minimum of two temperatures. This technique permits the selection for further optimization of lead ligands that bind to the target molecules with favorable enthalpies. Those ligands will exhibit higher solubilities in aqueous solution than ligands selected by conventional means, and may exhibit lower susceptibilities to resistant mutations. The method may be utilized as a standalone technique, or may be adapted to, for example, known high throughput screening technologies. The present invention further comprises an apparatus for carrying out the described methods.
Inventors:
FREIRE ERNESTO
TODD MATTHEW J
TODD MATTHEW J
Application Number:
PCT/US2000/042424
Publication Date:
January 17, 2002
Filing Date:
December 01, 2000
Export Citation:
Assignee:
UNIV JOHNS HOPKINS (US)
International Classes:
C12M1/34; C12Q1/00; C12Q1/68; G01N33/566; G01N33/15; G01N33/50; G01N33/53; G01N33/543; G01N37/00; (IPC1-7): G01N33/53; G01N33/566; G01N33/557
Other References:
LUQUE I. ET AL.: "Molecular basis of resistance to HIV-1 protease inhibition: A plausable hypothesis", BIOCHEMISTRY, vol. 37, 1998, pages 5791 - 5797, XP001020364
GOMEZ J. ET AL.: "Thermodynamic mapping of the inhibitor site of the aspartic protease endothiapepsin", JOURNAL OF MOLECULAR BIOLOGY, vol. 252, 1995, pages 337 - 350, XP002941144
GOMEZ J. ET AL.: "Thermodynamic mapping of the inhibitor site of the aspartic protease endothiapepsin", JOURNAL OF MOLECULAR BIOLOGY, vol. 252, 1995, pages 337 - 350, XP002941144
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