The biliproteins are a family of naturally occurring chromophores which are made up of linear tetrapyrrole derivatives covalently bonded to a protein residue. Representative examples include phytochrome (1), which functions as the """"""""on-off"""""""" switch for photomorphogenesis in higher plants, and phycocyanin (2), which is commonly found in eucaryotic algae and serves as a light harvesting protein. In addition to promoting seed germination and flowering, (1) has also been implicated in the control of potassium uptake, chloroplast movement and water permeability in green plant metabolism, and it is of particular interest due to its photoreversible-photochromic behavior. However, although the structure of the physiologically inactive Pr form is now reasonably well understood, little is known about the structure of the photoactivated Pfr form. In part this is due to the difficulty of preparing suitable model systems utilizing the available synthetic methodology in this area. In this proposal we attempt to address this deficiency by exploring a novel, and potentially highly efficient, synthetic route to the biliproteins and related materials. The approach described is a convergent one which offers excellent opportunities for the control of both relative and absolute stereochemistry, and it should be readily adaptable to the synthesis of porphyrins, corrins, and other biologically important macrocycles.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM038913-04A2
Application #
3295701
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1987-07-01
Project End
1995-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wesleyan University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Middletown
State
CT
Country
United States
Zip Code
06459
Dror, Shimshon Ben; Bronshtein, Irena; Garini, Yuval et al. (2009) The localization and photosensitization of modified chlorin photosensitizers in artificial membranes. Photochem Photobiol Sci 8:354-61
Ben Dror, Shimshon; Bronshtein, Irena; Weitman, Hana et al. (2009) The binding of analogs of porphyrins and chlorins with elongated side chains to albumin. Eur Biophys J 38:847-55
Wang, Hui; Tassa, Carlos; Jacobi, Peter A (2008) Toward the synthesis of cobyric acid. Enantioselective syntheses of completely differentiated ring D synthons. Org Lett 10:2837-40
O'Neal, William G; Jacobi, Peter A (2008) Toward a general synthesis of chlorins. J Am Chem Soc 130:1102-8
O'Neal, William G; Roberts, William P; Ghosh, Indranath et al. (2006) Studies in chlorin chemistry. 3. A practical synthesis of c,d-ring symmetric chlorins of potential utility in photodynamic therapy. J Org Chem 71:3472-80
O'Neal, William G; Roberts, William P; Ghosh, Indranath et al. (2005) Studies in chlorin chemistry. II. A versatile synthesis of dihydrodipyrrins. J Org Chem 70:7243-51
Jacobi, Peter A; Adel Odeh, Imad M; Buddhu, Subhas C et al. (2005) Synthetic Studies in Phytochrome Chemistry. Synlett :2861-2885
Jacobi, Peter A; Li, Yongkai (2003) Enantioselective syntheses of ring-C precursors of vit. B(12). Reagent control. Org Lett 5:701-4
Jacobi, Peter A; Tassa, Carlos (2003) Enantioselective syntheses of ring-C precursors of vitamin B12. Substrate control. A novel Si-assisted elimination of vinyl bromides. Org Lett 5:4879-82
Ghosh, Indranath; Jacobi, Peter A (2002) Lewis acid-promoted oxidative addition of thioimidates to Pd0. J Org Chem 67:9304-9

Showing the most recent 10 out of 17 publications