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.
Lee
Jiyong
J
Division of Translational Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Udugamasooriya
D Gomika
DG
Lim
Hyun-Suk
HS
Kodadek
Thomas
T
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