Natural and synthetic analogues of actinomycin D as Grb2-SH2 domain blockers

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Abstract

Natural analogues (D, C2, and VII) of actinomycin inhibit Grb2 SH2 domain binding with phosphopeptide-derived from Shc in vitro and in intracellular system. To study structure-activity relationships, 13 actinomycin analogues were synthesized and we found that the inhibition activity depended on the substituents of cyclic peptide groups in actinomycin and two analogues with Tyr residue are the most potent inhibitors with IC50 value of 0.5 and 0.8 μM, respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.

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Kim, H. K., Nam, J. Y., Han, M. Y., Son, K. H., Choi, J. D., Kwon, B. M., … Takusagawa, F. (2000). Natural and synthetic analogues of actinomycin D as Grb2-SH2 domain blockers. Bioorganic and Medicinal Chemistry Letters, 10(13), 1455–1457. https://doi.org/10.1016/S0960-894X(00)00258-4

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