Potent and selective photo-inactivation of proteins with peptoid-ruthenium conjugates.
Advances in high-throughput screening now enable the rapid discovery of bioactive small molecules, but these primary hits almost always exhibit modest potency. We report a strategy for the transformation of these hits into much more potent inhibitors without compound optimization. Appending a derivative of Ru(II)(tris-bipyridyl)(2+), an efficient photosensitizer of singlet oxygen production, to synthetic protein-binding compounds results in highly potent and specific target protein inactivation upon irradiation with visible light.
Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Jiyong
J
Lee
D Gomika
DG
Udugamasooriya
Hyun-Suk
HS
Lim
Thomas
T
Kodadek
D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008027:Light; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D034444:Peptoids / Q000737:chemistry* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D026082:Singlet Oxygen / Q000378:metabolism; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*
C533385:GU40C compound; D009942:Organometallic Compounds; D034444:Peptoids; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D012428:Ruthenium; D040301:Vascular Endothelial Growth Factor Receptor-2