The importance of vitamin A in health research is self-evident. During the past grant periods, we completed the synthesis of all 16 possible geometric isomers. Now, for the first part of the current proposal, we propose to prepare isomers and analogs of vitamin A2 and the pro-vitamin A, Beta-carotene. The proposed methodologies continue to be a combination of regioselective photoisomerization and standard thermal reactions. Besides synthetic sequences using building block already available in this laboratory, we also propose new routes using the pre- assembled (commercially available) all-trans isomer of vitamin A or carotenoids for their conversion to the less available hindred isomers. Ensuing photochemical studies are proposed aiming at a better understanding of the general properties of excited polyenes. Such knowledge is clearly important for prediction of photochemistry of polyenes, for synthetic applications and for a better understanding of the specific mode of reaction in natural polyene containing systems. For the second part, we propose to study properties of several retinal binding proteins and caroteno-proteins. The emphasis for the first group will be on preparation of those retinoids known to give exceptionally red-shifted absorption characteristics. These compounds and the resultant pigment analogs will provide a set of chemical standard for determining the threshold energies necessary for visual excitation, proton or chloride pumping activities in bacteriorhodopsin or halorhodopsin and photomovement in sensory rhodopsin. The study of the carotenoproteins will involve the preparation of a series of carotenoids (oxygenated and fluorinated) analogs to study the corresponding protein analogs spectroscopically (uv-vis and NMR). Results are expected to be useful for the proposed Zagalsky model for Beta-crustacyanin, constructed by molecular modeling from retinol binding proteins because of lack of crystal structural data on carotenoproteins. Information from the proposed studies is expected to lead to a general understanding on the role of the protein host in perturbing the absorption characteristics and modes of reaction of any protein bound polyene systems, and to assist the design of other new red-shifted systems in other areas of studies (e.g., material science). The new sets of retinoids and carotenoids will not only be useful for our own studies but also for other biochemical and pharmaceutical researches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK017806-24S1
Application #
6404925
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
May, Michael K
Project Start
1975-01-01
Project End
2002-01-31
Budget Start
1998-12-05
Budget End
2002-01-31
Support Year
24
Fiscal Year
2001
Total Cost
$64,403
Indirect Cost
Name
University of Hawaii
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Liu, Robert S H; Colmenares, Leticia U (2003) The molecular basis for the high photosensitivity of rhodopsin. Proc Natl Acad Sci U S A 100:14639-44
Liu, Robert S H (2002) Introduction to the symposium-in-print: photoisomerization pathways, torsional relaxation and the hula twists. Photochem Photobiol 76:580-3
Liu, R S; Hammond, G S (2001) Examples of hula-twist in photochemical cis- trans isomerization. Chemistry 7:4537-44
Liu, R S (2001) Photoisomerization by hula-twist: a fundamental supramolecular photochemical reaction. Acc Chem Res 34:555-62
Muthyala, R; Watanabe, D; Asato, A E et al. (2001) The nature of the delocalized cations in azulenic bacteriorhodopsin analogs. Photochem Photobiol 74:837-45
Liu, R S; Hammond, G S (2000) The case of medium-dependent dual mechanisms for photoisomerization: one-bond-flip and hula-twist. Proc Natl Acad Sci U S A 97:11153-8
Imai, H; Hirano, T; Terakita, A et al. (1999) Probing for the threshold energy for visual transduction: red-shifted visual pigment analogs from 3-methoxy-3-dehydroretinal and related compounds. Photochem Photobiol 70:111-5
Li, X Y; Liu, R S (1995) Photostationary state compositions of retinal and related compounds included in beta-lactoglobulin. Effects of protein host on isomer distribution of polyene substrates. Photochem Photobiol 62:361-6
Asato, A E; Peng, A; Hossain, M Z et al. (1993) Azulenic retinoids: novel nonbenzenoid aromatic retinoids with anticancer activity. J Med Chem 36:3137-47
Liu, R S; Krogh, E; Li, X Y et al. (1993) Analyzing the red-shift characteristics of azulenic, naphthyl, other ring-fused and retinyl pigment analogs of bacteriorhodopsin. Photochem Photobiol 58:701-5

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