1. Synthetic Mimetics of Actin-Binding Macrolides: Rational Design of Actin-Targeted Drugs 
Richard D. Perrins, Giuseppe Cecere, Ian Paterson, Gerard Marriott 
Chemistry & Biology 
Volume 15, Issue 3, Pages (March 2008)
DOI: /j.chembiol
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2. Figure 1 The Structures of Reidispongiolide A and the Tail Analogs
The chemical structures of reidispongiolide A (1) and the synthetic analogs based on the tail region of reidispongiolide (labeled as 2 through to 11). Modifications to the tail are highlighted in red. Carbon atom numbering is based on the scheme previously used for reidispongiolide (Allingham et al., 2005). The crystal structure of reidispongiolide A bound to G-actin (Allingham et al., 2005) is shown in the top left. SD1 is shown in blue, SD3 is shown in translucent red, and reidispongiolide is shown in CPK coloring.
Chemistry & Biology  , DOI: ( /j.chembiol )
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3. Figure 2
The Binding of Reidispongiolide and Related Compounds to Actin, Their Effect on Actin Polymerization, Depolymerization, Severing, and Competition with Other Actin-Binding Proteins
(A) Fluorescence emission spectra of 1 μM Prodan-G-actin in G-buffer and 1 μM Prodan-G-actin in G-buffer and 10 μM of compounds 1 though 11.
(B) Incubation of 0 to 50 μM 5 with 50 nM Prodan-G-actin in G-buffer.
(C) Binding of compounds 1 through 11 to Prodan-G-actin in G-buffer. The integrated emission spectra are normalized by using the integrated spectra of Prodan-G-actin obtained in the absence of compound and in conditions where the macrolide binding site of Prodan-G-actin is fully occupied by either the compound being titrated or halichondramide. The disassociation constants are shown in Table 1.
(D) Polymerization of 2 μM Prodan-G-actin in the absence or presence of 2 μM of either 5 or reidispongiolide (1) in polymerization buffer.
(E) Prodan-F-actin was diluted so that the total G-actin concentration was 0.1 μM, which is below the critical concentration where actin polymerization can occur. Therefore only loss of monomers from the (−)-end is possible. The rate of depolymerization in the presence of either 4 μM 5 or 0.3 μM reidispongiolide (1) is significantly quicker than with just F-actin on its own. This is strongly suggestive of F-actin severing by 5 and reidispongiolide.
(F) Displacement of CapG from Prodan-G-actin by 5.
Chemistry & Biology  , DOI: ( /j.chembiol )
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4. Figure 3
The Effect of Reidispongiolide and Tail Analogs 4, 5, 6, and 7 on Cultured NBT-II Cells
Micrographs of (A) untreated NBT-II epithelial cells and NBT-II cells treated with: (B) 10 nM, (C) 100 nM, (D) 1 μM, and (E) 10 μM reidispongiolide; (F) 10 nM, (G) 100 nM, (H) 1 μM, and (I) 10 μM tail analog 5; (J) 10 μM tail analog 4; (K) 10 μM tail analog 6; and (L) 10 μM tail analog 7.
Chemistry & Biology  , DOI: ( /j.chembiol )
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