deCODE Launches Fragments of Life™ Screening Technology

deCODE chemistry & biostructures, the contract drug discovery subsidiary of deCODE Genetics Inc., has introduced the Fragments of Life™ library consisting of 800 small molecules for fragment-based crystallographic screening.

The library is intended to serve as an additional tool to enhance deCODE’s contract drug discovery services by providing a starting point for lead discovery and inhibitor development.

The fragments in the library have been selected for pharmaceutical properties from conserved molecules of life, stable metabolites, known drug building blocks and fragments thereof, including synthetic intermediates that have evolved from deCODE’s chemistry labs over the past 15 years.

The concept guiding the development of the Fragments of Life™ library is that proteins have evolved to bind small molecules (metabolites) and other proteins within the cell.

A selection of molecules that can be found in living cells (metabolic intermediates, amino acids, etc.) forms the core of the Fragments of Life™ library.

Additional compounds were added to the library following a computer search of the Available Chemicals Directory which selected molecules that shared key physical properties (molecular weight, total polar surface area, cLogP, etc.) with the metabolites.

deCODE chemistry & biostructures is using fragment-based screening with the Fragments of Life™ to initiate lead discovery and development programs.

Hits acquired through the first round of screening will immediately be subjected to two parallel and complementary strategies of elaboration.

In the first approach, deCODE’s chemists will prepare derivatives of the lead fragments which will be assayed for improved binding affinity.

In a second approach, fragment hits will be re-pooled with other components of the library to identify secondary hits wherein a lead fragment comprises part of the secondary hit binding site.

Non-overlapping independent fragment hits can also be linked to achieve multiplicative gains in affinity.

Additional fragments can also be incorporated into pools, allowing the screen to be customized for individual targets.

For example, if the protein target is a metabolic enzyme, several fragments will be chosen that represent precursors, intermediates and derivatives of the enzyme’s substrate and product molecules.

Compilation of data from elaborated and linked lead fragments from this integrated process will allow development of high affinity drug candidate molecules.