TY - JOUR
T1 - The chemistry-medicine continuum
T2 - Synthetic, computer, spectroscopic and biological studies on new chemotherapeutic leads
AU - Wender, Paul A.
AU - Martin-Cantalejo, Yolanda
AU - Carpenter, Andrew J.
AU - Chiu, Anna
AU - De Brabander, Jef
AU - Harran, Patrick G.
AU - Jimenez, Juan Miguel
AU - Koehler, Michael F T
AU - Lippa, Blaise
AU - Morrison, James A.
AU - Müller, Stephan G.
AU - Müller, Stephan N.
AU - Park, Cheol Min
AU - Shiozaki, Makoto
AU - Siedenbiedel, Carsten
AU - Skalitzky, Donald J.
AU - Tanaka, Masahiro
AU - Irie, Kazuhiro
N1 - Funding Information:
Acknowledgments: Support of this work through a grant (CA31845) provided by the National Institutes of Health (P.A.W.), a Grant-in-Aid for Scientific Research on Priority Areas (No. 08219224), and Scientific Research (C) (No. 0866013 7) from the Ministry of Education, Science, and Culture, Japan (K.I.) are gratefully acknowledged. HRMS analyses were performed at the University of California, San Francisco Regional and the University of California, Riverside Mass Spectrometry Facilities. Fellowship support from the following institutions is also gratefully recognized: Fulbright / Spanish Ministry of Education and Science (J.M.J., Y.M-C.), American Cancer Society (A.J.C.), Bing Foundation (A.C.), Fulbright-Hays / NATO (J.D.B.), NIH (P.G.H., J.A.M.), Eli Lilly (M.F.T.K.), Deutsche Forschungsgemeinschaft (S.G.M.), Swiss National Science Foundation / Ciba-Geigy-Jubilaums-Stiftung (S.N.M.), the Korean Science and Engineering Foundation (C-M.P.), Japan Tobacco (M.S., M.T.), and the Alexander von Humboldt Foundation (C.S.).
PY - 1998/3
Y1 - 1998/3
N2 - This lecture provides an overview of investigations directed towards understanding the molecular mechanism of protein kinase C (PKC) activation and function. Central to this effort are studies on the total synthesis of phorbol, the first asymmetric synthesis of phorbol, and the first synthesis of resiniferatoxin, all involving highly effective applications of [5+2] oxidopyrylium-alkene cycloadditions. The synthesis and affinities of the phorbol ester binding domain of PKC are also presented. In addition, a pharmacophore model for agonist binding to PKC is presented in connection with the design of novel PKC activators. Finally, the computer modeling, NMR structure, synthesis, and biological activity of the first fully synthetic bryostatin analogs are described.
AB - This lecture provides an overview of investigations directed towards understanding the molecular mechanism of protein kinase C (PKC) activation and function. Central to this effort are studies on the total synthesis of phorbol, the first asymmetric synthesis of phorbol, and the first synthesis of resiniferatoxin, all involving highly effective applications of [5+2] oxidopyrylium-alkene cycloadditions. The synthesis and affinities of the phorbol ester binding domain of PKC are also presented. In addition, a pharmacophore model for agonist binding to PKC is presented in connection with the design of novel PKC activators. Finally, the computer modeling, NMR structure, synthesis, and biological activity of the first fully synthetic bryostatin analogs are described.
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U2 - 10.1351/pac199870030539
DO - 10.1351/pac199870030539
M3 - Article
AN - SCOPUS:0001486312
SN - 0033-4545
VL - 70
SP - 539
EP - 546
JO - Pure and Applied Chemistry
JF - Pure and Applied Chemistry
IS - 3
ER -