SAR by MS: a ligand based technique for drug lead discovery against structured RNA targets

Eric E Swayze; Elizabeth A Jefferson; Kristin A Sannes-Lowery; Lawrence B Blyn; Lisa M Risen; Satoshi Arakawa; Stephen A Osgood; Steven A Hofstadler; Richard H Griffey

doi:10.1021/jm0255466

SAR by MS: a ligand based technique for drug lead discovery against structured RNA targets

J Med Chem. 2002 Aug 29;45(18):3816-9. doi: 10.1021/jm0255466.

Authors

Eric E Swayze¹, Elizabeth A Jefferson, Kristin A Sannes-Lowery, Lawrence B Blyn, Lisa M Risen, Satoshi Arakawa, Stephen A Osgood, Steven A Hofstadler, Richard H Griffey

Affiliation

¹ Ibis Therapeutics, A Division of Isis Pharmaceuticals, Inc., 2292 Faraday Avenue, Carlsbad, California 92008, USA. eswayze@isisph.com

PMID: 12190303
DOI: 10.1021/jm0255466

Abstract

A technique for lead discovery vs RNA targets utilizing mass spectrometry (MS) screening methods is described. The structure-activity relationships (SAR) derived from assaying weak binding motifs allows the pharmacophores discovered to be elaborated via "SAR by MS" to higher affinity ligands. Application of this strategy to a subdomain of the 23S rRNA afforded a new class of compounds with functional activity.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Amino Acids / chemistry
Ligands
Mass Spectrometry
Quantitative Structure-Activity Relationship*
Quinoxalines / chemistry
RNA / chemistry*
Stereoisomerism

Substances

Amino Acids
Ligands
Quinoxalines
RNA