Session TOA. There are 3 abstracts in this session.

Session: Small Molecules 2, time: 08:30am-09:10am

Drug discovery aided by NMR- and enthalpy-based screening of combinatorial libraries

Maurizio Pellecchia
University of California, Riverside, CA
We demonstrated that focused combinatorial libraries, arranged in positional scanning fashion (POS), can be screened by NMR (HTS by NMR) allowing the identification of initial antagonists of protein-protein interactions (PPIs). A powerful extension of the method consists of derivatizing a known binding scaffold with a POS library. Screening of such focused-POS libraries (fPOS) can be accomplished by NMR revealing a high population of high affinity ligands. To this end we also found that for fPOS libraries, enthalpy measurements can be effectively used as complementary screening or pre-screening approach. I will report on our recent examples where by the HTS by NMR and the enthalpy screening methods have resulted in the identification of unique, potent agents against a variety of PPIs.

Session: Small Molecules 2, time: 09:10am-09:50am

Exploring a New Therapeutic Target Space: Can One Design Small Molecule Drugs for RNA?

Jasna Fejzo
UMass Amherts, Amherst, MA
Most of the human genome encodes RNAs that do not code for proteins. Non-coding RNAs may affect normal gene expression and disease progression, suggesting a new class of untapped targets for drug discovery.
We have structural information on RNA, we know there are drugable sites, yet developing small molecule drugs for RNA has been a tremendous challenge. RNA is inherently flexible and due to this flexibility X-ray fails to provide the structural information required for RNA drug design and optimization. We have used NMR to detect binding and to derive a limited number of important structural constraints that have successfully guided modeling and chemistry optimization. We present examples where, using this approach, small molecule selective RNA binders have been identified.

Session: Small Molecules 2, time: 09:50am-10:30am

NMR Supersequences for the Characterisation of Small Molecules

Tim Claridge1; Eriks Kupce2
1University of Oxford, Oxford, United Kingdom; 2Bruker UK, Coventry, United Kingdom
The structure characterisation of small molecules by NMR spectroscopy continues to represent one of the major applications of this analytical technique and routinely employs well established 2D homonuclear and heteronuclear correlation experiments. Now recognised as the leading techniques, attention has turned to developing experimental methods that allow the faster collection of these data sets. Herein, we describe an approach to data collection we term NOAH (NMR by Ordered Acquisition using 1H-detection) that records multiple 2D data sets nested as modules within a single “supersequence”. This requires only a single recovery delay for each series of modules, and so allows for significantly reduced data collection times.