The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.
 

The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.

Related Articles The SHAPES strategy: an NMR-based approach for lead generation in drug discovery.

Chem Biol. 1999 Oct;6(10):755-69

Authors: Fejzo J, Lepre CA, Peng JW, Bemis GW, Ajay , Murcko MA, Moore JM

BACKGROUND: Recently, it has been shown that nuclear magnetic resonance (NMR) may be used to identify ligands that bind to low molecular weight protein drug targets. Recognizing the utility of NMR as a very sensitive method for detecting binding, we have focused on developing alternative approaches that are applicable to larger molecular weight drug targets and do not require isotopic labeling. RESULTS: A new method for lead generation (SHAPES) is described that uses NMR to detect binding of a limited but diverse library of small molecules to a potential drug target. The compound scaffolds are derived from shapes most commonly found in known therapeutic agents. NMR detection of low (microM-mM) affinity binding is achieved using either differential line broadening or transferred NOE (nuclear Overhauser effect) NMR techniques. CONCLUSIONS: The SHAPES method for lead generation by NMR is useful for identifying potential lead classes of drugs early in a drug design program, and is easily integrated with other discovery tools such as virtual screening, high-throughput screening and combinatorial chemistry.

PMID: 10508679 [PubMed - indexed for MEDLINE]



Source: PubMed