MULTIPLEX SG CAP PLATFORM-BASED DRUG LEAD DISCOVERY USING FOCUSED PLANT CELL CULTURE LIBRARY: EFFICIENT SCREENING TECHNOLOGY FOR INHIBITORS OF PROTEIN-PROTEIN INTERACTIONS USING SOL-GEL ENTRAPMENT OF PLANT CELL CULTURE EXTRACTS

Jennifer Normanly, Yong Zhang, Sergey Savinov, Li-Jun Ma, Elizabeth Vierling, Kyung Hoon Hwang, Hyun Ji Park, Joo Young Bang and Soyoun Kim

UMass Amherst BioFoundry, Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, USA

Abstract

Protein-protein interactions (PPIs) are druggable targets that expand drug discovery opportunities. Conventional screening methods are challenging for PPIs because interacting surfaces may be too large for small molecules, and the shortage of reliable multiplex immobilization platforms. PCL’s SG Cap is a sol-gel based technology that captures a variety of molecules inside specially engineered 3D nanopore structures without the use of affinity tags, linkers, or other modifications. Native conformations and active sites of proteins are preserved, making it a powerful tool for screening and other applications. The UMass Amherst BioFoundry’s Plant Cell Culture Library (PCCL, http://pccl.library.umass.edu/research.html) is a collection of 2200 unique plant species with enormous chemical diversity. We used PCL’s SG Cap technology to screen 88 methyl jasmonate-elicited plant cell extracts for antagonism of vascular endothelial growth factor (VEGF) - VEGF receptor (VEGFR) contact, an established target for anticancer interventions. Two confirmed hits from replicate tests diminished the VEGF-VEGFR interaction in a concentration- and elicitation-dependent manner, indicating that, i) the PCCL is a suitable source of chemodiversity to tackle perturbation of protein–protein interactions and ii) PCL’s SG Cap is an effective discovery platform for the inhibitors of protein-protein interactions.

REFERENCE

Kim, S., et al., (2006) Anal. Chem., 78, 7392-7396.