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Potent and selective photo-inactivation of proteins with peptoid-ruthenium conjugates.

ABSTRACT: 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.

SUBMITTER: Lee J

PROVIDER: S-EPMC3049443 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Potent and selective photo-inactivation of proteins with peptoid-ruthenium conjugates.

Lee Jiyong J Udugamasooriya D Gomika DG Lim Hyun-Suk HS Kodadek Thomas T

Nature chemical biology 20100314 4

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 ...[more]

PMID: 20228793

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