There is increasing interest in the development of covalent ligands of proteins, which have many advantages over non-covalent ligands. The goal of this proposal is to develop large libraries of DNA-encoded libraries of potential covalent ligands and to optimize methods to screen them. This would represent a major advance over current technology to identify covalent ligands, which almost always relies on structure-aided grafting of an electrophile onto an existing reversible ligand. The successful completion of this Phase I effort would establish a platform that Deluge could offer customers in the form of a custom screening service for the identification of potent and selective covalent ligands for any protein of interest to the customer that has surface-accessible cysteines.

Public Health Relevance

There is increasing intense interest in the discovery of drug leads that engage protein targets covalently, since they generally display higher potency and longer residence times than non-covalent ligands. We will optimize protocols to create and screen a DNA-encoded library of about three million novel compounds, all containing an ?-cyanoacrylamide warhead that reacts covalently, but reversibly, with cysteine thiols. The goal at the conclusion of this Phase I effort will be to establish a streamlined operation that can be offered to customers as a custom screening service.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM134785-01
Application #
9846321
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Anderson, Vernon
Project Start
2019-09-01
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Deluge Biotechnologies, Inc.
Department
Type
DUNS #
City
Jupiter
State
FL
Country
United States
Zip Code
33458