ACS Combinatorial Science
Letter
A.; Robinett, R. G.; Shearin, J.; Spearing, P. K.; Stewart, E. L.;
Turnbull, P. S.; Weaver, S. L.; Williams, S. P.; Wisely, G. B.; Lambert.,
M. H. A New Series of Estrogen Receptor Modulators That Display
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(6) Moon, H. S.; Jacobson, E. M.; Khersonsky, S. M.; Luzung, M. R.;
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W.; Rosania, G. R.; Schier, A. F.; Chang, Y. T. A Novel Microtubule
Destabilizing Entity from Orthogonal Synthesis of Triazine Library
and Zebrafish Embryo Screening. J. Am. Chem. Soc. 2002, 124, 11608−
11609.
(7) Williams, D.; Jung, D. W.; Khersonsky, S. M.; Heidary, N.;
Chang, Y. T.; Orlow, S. J. Identification of Compounds that Bind
Mitochondrial F1F0 ATPase by Screening a Triazine Library for
Correction of Albinism. Chem. Biol. 2004, 11, 1251−1259.
(8) Khersonsky, S. M.; Jung, D. W.; Kang, T. W.; Walsh, D. P.;
Moon, H. S.; Jo, H.; Jacobson, E. M.; Shetty, V.; Neubert, T. A.;
Chang, Y. T. Facilitated Forward Chemical Genetics Using Tagged
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(9) Guo, Z.; Wu, D.; Zhu, Y. F.; Tucci, F. C.; Pontillo, J.; Saunders, J.;
Xie, Q.; Struthers, R. S.; Chen, C. A. Convenient One-pot Synthesis of
Asymmetric 1,3,5-Triazine-2,4,6-triones and its Application Towards a
Novel Class of Gonadotropin-releasing Hormone Receptor Antago-
nists. Bioorg. Med. Chem. Lett. 2005, 15, 693−698.
amount of biochemically extracted TAG was quantified by
densitometry on iodine-stained TLC plates, and corroborated
the results obtained by fluorescence staining. These results
proved the application of 4,6-diaryl 1,3,5-triazines as candidate
molecules to increase lipid accumulation in Y. lipolytica.
In conclusion, we prepared in solid-phase a collection of 4,6-
diaryl and 4-aryl, 6-alkyl 1,3,5-triazines using Grignard reactions
and Suzuki couplings and performed an unbiased phenotypic
screening to discover E4 as a unique small molecule with
efficient biolipid generation activity. Further biochemical
studies toward target identification and mechanism elucidation
will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
■
S
Synthetic procedures for the library synthesis, characterization
data for the hit compounds and procedures for the bioassays.
This material is available free of charge via the Internet at
AUTHOR INFORMATION
Corresponding Author
■
T.C.). fax: +82 542792199 (Y.L.), +65 67791691 (Y.-T.C.).
Phone: +82 542792296 (Y.L.), +65 65166774 (Y.-T.C.).
(10) Balboni, G.; Lazzari, I.; Trapella, C.; Negri, L.; Lattanzi, R.;
Giannini, E.; Nicotra, A.; Melchiorri, P.; Visentin, S.; De Nuccio, C.;
Salvadori, S. Triazine Compounds as Antagonists at Bv8-Prokineticin
Receptors. J. Med. Chem. 2008, 51, 7635−7639.
Present Address
⊗The Scripps Research Institute, SR207 10550 North Torrey
Pines Road, SR202 La Jolla, CA 92037.
́
́ ́
(11) Krecmerova, M.; Holy, A.; Pískala, A.; Masojídkova, M.; Andrei,
G.; Naesens, L.; Neyts, J.; Balzarini, J.; Clercq, E.; De; Snoeck, R.
Antiviral Activity of Triazine Analogues of 1-(S)-[3-Hydroxy-2-
(phosphonomethoxy)propyl]cytosine (Cidofovir) and Related Com-
pounds. J. Med. Chem. 2007, 50, 1069−1077.
Author Contributions
#These authors contributed equally to this work.
Author Contributions
(12) Kido, H.; Goodrow, M. H.; Griffeth, V.; Lucas, A. D.; Gee, S. J.;
Hammock, B. D. Development of an Enzyme-linked Immunosorbent
Assay for the Detection of Hydroxytriazines. J. Agric. Food Chem. 1997,
45, 414−424.
(13) Lippa, K.; Roberts, A. Nucleophilic Aromatic Substitution
Reactions of Chloroazines with Bisulfide (HS-) and Polysulfides (Sn2-
). Environ. Sci. Technol. 2002, 36, 2008−2018.
Y.S.L. and Y.T.C. conceived and designed the research and
wrote the manuscript. J.Y.H.K. performed the biological
experiments and wrote the manuscript. J.W.L., W. S.L., H.-
H.H., and M.V. performed organic synthesis and wrote the
manuscript. J.T.B. carried out organic synthesis. All authors
have given approval to the final version of the manuscript.
(14) Chen, Y.; Wang, D. X.; Huang, Z. T.; Wang, M. X. Synthesis,
Structure, and Functionalization of Homo Heterocalix[2]arene[2]-
triazines: Versatile Conformation and Cavity Structures Regulated by
the Bridging Elements. J. Org. Chem. 2010, 75, 3786−3796.
(15) Umali, A. P.; Crampton, H. L.; Simanek, E. E. Triazine
Dendrimers with Orthogonally Protected Amines on the Periphery.
Masking Amines with Dde and BOC Groups Provides an Alternative
to Carrying Protected Alcohols and Disulfides through an Iterative
Synthesis. J. Org. Chem. 2007, 72, 9866−9874.
Funding
The authors are grateful to A*STAR SSCC Grant (SSCC10/
024) and the Global Frontier Program (2010-0029723) of the
Ministry of Education, Science and Technology of Korea for
the financial support.
Notes
The authors declare no competing financial interest.
(16) Lim, J.; Mintzer, M. A.; Perez, L. M.; Simanez, E. E. Synthesis of
Odd Generation Triazine Dendrimers Using a Divergent, Macro-
monomer Approach. Org. Lett. 2010, 12, 1148−1151.
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