3-dimensional Pharmaceuticals, Inc.

Eugenio C Petrella

Michael W Pantoliano

Barry A Springer

Francis Raymond Salemme

F Raymond Salemme

Alexander W Rhind

The present invention provides a method for ranking the affinity of each of a multiplicity of different molecules for a target molecule which is capable of unfolding due to a thermal change. The method comprises (a) contacting the target molecule with one molecule of a multiplicity of different molecules, in the presence of a 5-(4&Prime;-dimethylaminopheny-2-(4&prime;-phenyl)oxazole derivative dye, in each of a multiplicity of containers; (b) simultaneously heating the multiplicity of containers; (c) measuring the fluorescence in each of the containers; (d) generating thermal unfolding information for the target molecule as a function of temperature for each of the containers; (e) comparing the thermal unfolding information obtained for each of the containers to the thermal unfolding information for the target molecule in the absence of any of the molecules in the multiplicity of different molecules; and (f) ranking the affinities of each of the molecules according to the difference in the thermal unfolding information between the target molecule in each of the containers and the target molecule in the absence of any of the molecules in the multiplicity of different molecules.

Microplate thermal shift assay for ligand development using 5-(4&Prime;dimethylaminophenyl)-2-(4&prime;-phenyl)oxazole derivative fluorescent dyes

The present invention is a method for ranking the affinity of each of a multiplicity of different molecules for a target molecule which is capable of denaturing due to a thermal change. The method comprises contacting the target molecule with one molecule of the multiplicity of different molecules in each of a multiplicity of containers, simultaneously heating the multiplicity of containers, measuring in each of the containers a physical change associated with the thermal denaturation of the target molecule resulting from the heating in each of the containers, generating a thermal denaturation curve for the target molecule as a function of temperature for each of the containers and determining a midpoint temperature (T,) therefrom, comparing the T,of each of the thermal denaturation curves with the T,of a thermal denaturation curve obtained for the target molecule in the absence of any of the molecules in the multiplicity of different molecules, and ranking the affinities of the multiplicity of different molecules according the change in T,of each of the thermal denaturation curves.

Method for identifying conditions that facilitate recombinant protein folding

Microplate thermal shift assay for ligand development and multi-variable protein chemistry optimization

Method for determining conditions that facilitate protein crystallization

Method for determining conditions that stabilize proteins

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Wayne, PA, United States of America

Eugenio C Petrella