Lead and Probe Discovery Services

A gradient of orange and red test tubes

The Lead and Probe Discovery Core is a full-service combinatorial chemistry group that specializes in the optimization of compounds that are confirmed as active hits from high throughput screening. The process of optimization employed by the LPD features a cycle of design, synthesis, purification, and assay.

The LPD uses the tools of cheminformatics and the principles of medicinal chemistry to design arrays of follow up compounds based on the structures of the confirmed actives. These arrays help the medicinal chemists in the LPD develop structure-activity and structure-physical property relationships (SAR, SPR) between analogs of the confirmed hits. These arrays are synthesized using the parallel chemistry equipment available in the LPD. Compounds are purified in our high throughput purification group and are made available in plates for screening. Assay results in the form of SAR and SPR guide subsequent iterations of the optimization cycle, allowing the effective and rapid follow up of multiple active series.

Core Capabilities

  • Design, synthesis, purification and analysis of novel chemical libraries of from 24-200 compounds on a 5-100 mg scale.
  • Combinatorial medicinal chemistry
  • Automated and semi-automated solid- and solution-phase parallel synthesis capabilities
  • Rapid high throughput purification and analysis Analytical QA/QC is performed using a Waters uPLC outfitted with reverse-phase columns and having PDA (photodiode array), ELS (evaporative light-scattering), and MS detectors. Preparative separations are performed on a Waters Autopurify system equipped with a Waters 2767 Sample Manager and PDA and MS detectors. Rapid purification of arrays is facilitated by employing mass guided fractionation. The high throughput purification group is also equipped with a Bohdan Automator robotic balance for sample weighing and a Gilson 215 liquid-handling robot for sample preparation.
  • 4,750 sq ft of laboratory and office space
  • State-of-the-art analytical laboratory Chemoinformatics Tools employed in the Lead and Probe Discovery Core
  • IDBS ActivityBase: compound management and tracking
  • Cambridgesoft E-notebook: secure information tracking
  • Pipeline Pilot (Accelrys): product enumeration, in silico property prediction, lead-hopping
  • Spotfire (Perkin-Elmer): visualization of data, compound multi-parametric optimization


Michael A. Walters, Ph.D.
Director, Lead and Probe Discovery Core
Telephone: 612-626-6864
Fax: 612-626-6862
Email: [email protected]