David L. Van VrankenProfessor, Chemistry |
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| URL | chem.ps.uci.edu/~dlvanvra/DVVWWW.html | |
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Academic Distinctions |
National Science Foundation Postdoctoral Fellow Camille and Henry Dreyfus Foundation New Faculty Award National Science Foundation CAREER Award Glaxo Wellcome Chemistry Scholar Eli Lilly Faculty Grantee Alfred P. Sloan Research Fellow< br> Arthur C. Cope Scholar |
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| Appointments |
1991 - 1994 University of California at Berkeley Joined UCI faculty in 1994/ |
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Research Abstract |
Organic synthesis is a precision tool for engineering molecules and we are using organic synthesis to construct complex molecules: bioactive natural products, models of cross-linked proteins, and probes of biological function. Proteins are chemically reactive. Two biologically important patterns of reactivity are (i) the formation of carbon-carbon bonds between aromatic sidechains, and (ii) the covalent attachment of carbohydrates to protein sidechains. These reactions of peptides and proteins are an important guide for the construction of complex natural products and we have used them in the synthesis of the tjipanazoles, the peronatins, and the AT2433 antitumor natural products. As we continue to harness the reactions of amino acids for organic synthesis, we are also interested in the biological consequences of these reactions. Ditryptophan crosslinks can enforce 90 turns in peptide chains and induce peptides to crystallize in antiparallel beta sheets. In the defensin indolicidin, a ditryptophan crosslink confers protease resistance without diminution of the biological activity. The profound effects of ditryptophans have inspired us to look at the effects of dityrosine crosslinks, which are commonly found in long-lived structural human proteins.
Why synthesize complex molecules? In th e best of cases, complex molecules can serve as powerful tools for exploring biology and modulating biological function. The ability of tryptophan dimers to stereoselectively trap complex carbohydrates provides an efficient route to indolocarbazole gl ycoside natural products. Under physiological conditions, similar reactions graft glucose molecules onto human proteins, without the benefit of enzymatic control. These reactions are believed to contribute to the long-term consequences of diabetes: blindness, kidney failure, and amputation. The natural product bakuchiol, isolated from the Chinese herbal medicine buguzhi has been shown to reduce hyperglycemia in the db/db mouse model. Nothing is known about the origin of this important effect. We have developed a powerful itranscriptional control. Patents: Trost, B.M.; Van Vranken, D. L.; Bunt, R. L. "Asymmetric ligands useful for transition metal catalyzed bond forming reactions" 1998 U.S. Patent 5,739,396.ron-catalyzed reaction for constructing the hindered quaternary center of bakuchiol and related meroterpenoids. The structure and biological effects of bakuchiol resemble those of retinoids, suggesting a possible effect on t |
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| Publications | "Synthesis and Isomerization of Biindolinones from Collybia peronata and Tricholoma scalpturatum" Stachel SJ, Nilges M, Van Vranken DL J. Org. Chem. 1997, 62, 4756. | |
| "A Caveat in the Application of the Exciton Chirality Method to N,N-Dialkylamides. Synthesis and Structural Revision of AT2433-B1," Chisholm, J. D.; Golik, J.; Krishnan, B.; Matson, J. A.; Van Vranken, D. L. J. Am. Chem. Soc. 1999, 121, 3801. | ||
| "The Fluorescence of Scorpions and Cataractogenesis," Stachel, S. J.; Stockwell, S. A.; Van Vranken, D. L. Chemistry & Biology 1999, 6, 531. | ||
| "Regiocontrolled Synthesis of the Antitumor Antibiotic AT2433-A1," Chisholm, J. D.; Van Vranken, D. L. J. Org. Chem. 2000, 65, 7541-7553. | ||
| "Synthesis of ()-Madindolines and Chemical Models Studies of Chemical Reactivity." McComas CC, Perales JB, Van Vranken DL Org Lett 2002, 4, in press. | ||
| "Synthesis and Study of a Gramicidin B Mutant Possessing a Ditryptophan Crosslink." Presley Bodnar, AL, Gilbert EJ, Yoburn JC, Van Vranken DL J. Peptide Sci. 2002, in press. | ||
| "DNA sequence recognition by the indolocarbazole antitumor antibiotic AT2433-B1 and its diastereoisomer" Carrasco C, Facompr M, Chisholm JD, Van Vranken, DL, Wilson DW, Bailly C Nuc. Acids Res. 2002, 30, 1774. | ||
| "Intramolecular Ditryptophan Crosslinks Enforce Two Types of Antiparallel Beta Structures" Matthews JH, Dinh TD, Tivitmahaisoon P, Ziller JW, Van Vranken, DL Chemistry & Biology 2001, 8, 1071. | ||
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Professional Society |
American Chemical Society |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2091 | |
| Last updated | 10/14/2004 | |
