ACS Medicinal Chemistry Letters
Letter
(12) Lin, J.; Yang, Q.; Wilder, P. T.; Carrier, F.; Weber, D. J. The
calcium-binding protein S100B down-regulates p53 and apoptosis in
malignant melanoma. J. Biol. Chem. 2010, 285, 27487−27498.
(13) Lin, J.; Yang, Q.; Yan, Z.; Markowitz, J.; Wilder, P. T.; Carrier,
F.; Weber, D. J. Inhibiting S100B restores p53 levels in primary
malignant melanoma cancer cells. J. Biol. Chem. 2004, 279, 34071−
34077.
(14) Charpentier, T. H.; Wilder, P. T.; Liriano, M. A.; Varney, K. M.;
Pozharski, E.; MacKerell, A. D., Jr.; Coop, A.; Toth, E. A.; Weber, D. J.
Divalent metal ion complexes of S100B in the absence and presence of
pentamidine. J. Mol. Biol. 2008, 382, 56−73.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details for heptamidine synthesis, computational
methods, protein growth and purification, cellular assays, and
NMR and DSC as well as figures for additional MD
simulations, HSQC of 15N S100B, crystal and refinement
statistics, and a close view of the compound binding sites. This
material is available free of charge via the Internet at http://
(15) Smith, J.; Stewart, B. J.; Glaysher, S.; Peregrin, K.; Knight, L. A.;
Weber, D. J.; Cree, I. A. The effect of pentamidine on melanoma ex
vivo. Anticancer Drugs 2010, 21, 181−185.
(16) Markowitz, J.; Chen, I.; Gitti, R.; Baldisseri, D. M.; Pan, Y.;
Udan, R.; Carrier, F.; MacKerell, A. D., Jr.; Weber, D. J. Identification
and characterization of small molecule inhibitors of the calcium-
dependent S100B-p53 tumor suppressor interaction. J. Med. Chem.
2004, 47, 5085−5093.
AUTHOR INFORMATION
Corresponding Author
Author Contributions
All authors have given approval to the final version of this
manuscript.
■
(17) Bodenhausen, G. R.; Ruben, D. J. Natural abundance nitrogen-
15 NMR by enhanced heteronuclear spectroscopy. Chem. Phys. Lett.
2002, 69, 185−189.
Funding
This work was supported by grants from the NIH (GM58888
and CA107331) to D.J.W.
Notes
The authors declare no competing financial interest.
ABBREVIATIONS
■
NMR, nuclear magnetic resonance; HSQC, heteronuclear
single quantum coherence; MD, molecular dynamics; LD50,
lethal dose for 50% of the population; DSC, differential
scanning calorimetry
REFERENCES
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