University of South Florida

The Penn State Research Foundation

Kenichiro Doi

Roman Manetsch

David Lawrence Flanigan

Hong-Gang Wang

Jeremiah Dwayne Tipton

Katya Pavlova Nacheva

Niranjan Kumar Namelikonda

Megan M Barber

Iredia David Iyamu

Sameer Shamrao Kulkarni

Methods of identifying target binding molecules by target guided synthesis are provided. The methods include providing two or more fragments capable of reacting to form the target binding molecule and mixing the fragments with the target. The methods can be used to identify target binding molecules that bind targets such as proteins or nucleic acids, including those that bind shallow binding pockets on the surface of such targets. The methods are applied to the Bcl-XL and Mcl-1 proteins from the Bcl-2 family of proteins. Using thio acid and sulfonyl azide fragments capable of reacting through sulfo-click chemistry, new acyl sulfonamides are identified that bind one or both of the Bcl-XL and Mcl-1 proteins. Pharmaceutical formulations of these target binding molecules are also provided.

Target binding molecules identified by kinetic target-guided synthesis

Growing community of inventors

Hummelstown, PA, United States of America

Kenichiro Doi