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. 2016 Oct 11;138(43):14303–14311. doi: 10.1021/jacs.6b07440

Figure 1.

Figure 1

Use of fluorescence-based thermal shift assay to detect small molecules capable of inducing dehomooliogomerization. (a) Hypothetical scheme illustrating whether small-molecule (triangle) disruption of a homodimeric assembly (black) to a monomeric state (red) is translated to a negative thermal shift. The first derivative of the melting curves are shown. (b) Schematic showing the undecameric-to-dimeric transition of Rad521–209 induced by 6-hydroxydopa (green). (c) Rad521–209 alone (blue) did not produce a melting transition, indicating that its Tm was more than 99 °C. In the presence of 6-hydroxydopa, Rad521–209 registered a Tm of 85.0 °C (red). (d) SPD304 (blue) causes the dissociation of native trimeric TNF-α (purple) into a SPD304–bound dimer (pink) and monomer (yellow). (e) The melting curve of native trimeric TNF-α (purple) showed that it had a putative Tm of 65 °C. In the presence of SPD304, the melting temperature of TNF-α decreased to 61.0 °C (pink). (f) Distribution of thermal shift values induced by fragments in CK2β from the fluorescence-based thermal shift screen.