SAR by MS: a ligand based technique for drug lead discovery against structured RNA targets.
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.
Swayze
Eric E
EE
Ibis Therapeutics, A Division of Isis Pharmaceuticals, Inc., 2292 Faraday Avenue, Carlsbad, California 92008, USA. eswayze@isisph.com
Jefferson
Elizabeth A
EA
Sannes-Lowery
Kristin A
KA
Blyn
Lawrence B
LB
Risen
Lisa M
LM
Arakawa
Satoshi
S
Osgood
Stephen A
SA
Hofstadler
Steven A
SA
Griffey
Richard H
RH
D000596:Amino Acids / Q000737:chemistry; D008024:Ligands; D013058:Mass Spectrometry; D021281:Quantitative Structure-Activity Relationship; D011810:Quinoxalines / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D008024:Ligands; D011810:Quinoxalines; D012313:RNA