Abstract

We have established that phaeomelanin is photolabile under biologically significant conditions. We believe that there are several mechanisms by which this observation could account for the increased sensitivity to ultraviolet light exhibited by people of Celtic ancestry. In order to test our hypotheses it is necessary to characterize the photodegradation products of phaeomelanin. To aid in this task we propose to undertake the synthesis and photolysis of several model compounds. The question of the detailed structure of phaeomelanin further complicates analysis of its photodegradation and we propose to reinvestigate the structure by a combination of chemical modifications and modern spectroscopic techniques. It is the primary goal of this proposal to isolate and characterize the photolysis products of phaeomelanin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG002380-06S1
Application #
3114427
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1980-01-01
Project End
1985-10-31
Budget Start
1985-08-01
Budget End
1985-10-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Sonnen, J A; Larson, E B; Walker, R L et al. (2010) Nonsteroidal anti-inflammatory drugs are associated with increased neuritic plaques. Neurology 75:1203-10
Haneuse, Sebastien; Larson, Eric; Walker, Rod et al. (2009) Neuropathology-based risk scoring for dementia diagnosis in the elderly. J Alzheimers Dis 17:875-85
Lambert, C; Chacon, J N; Chedekel, M R et al. (1989) A pulse radiolysis investigation of the oxidation of indolic melanin precursors: evidence for indolequinones and subsequent intermediates. Biochim Biophys Acta 993:12-20
Chedekel, M R; Zeise, L (1988) Sunlight, melanogenesis and radicals in the skin. Lipids 23:587-91
Chedekel, M R; Subbarao, K V; Bhan, P et al. (1987) Biosynthetic and structural studies on pheomelanin. Biochim Biophys Acta 912:239-43
Koch, W H; Chedekel, M R (1987) Photogeneration of free radicals from eumelanogenic intermediates and metabolites. Biochim Biophys Acta 924:458-66
Land, E J; Thompson, A; Truscott, T G et al. (1986) Photochemistry of melanin precursors: dopa, 5-S-cysteinyldopa and 2,5-S,S'-dicysteinyldopa. Photochem Photobiol 44:697-702
Koch, W H; Chedekel, M R (1986) Photoinitiated DNA damage by melanogenic intermediates in vitro. Photochem Photobiol 44:703-10
Thompson, A; Land, E J; Chedekel, M R et al. (1985) A pulse radiolysis investigation of the oxidation of the melanin precursors 3,4-dihydroxyphenylalanine (dopa) and the cysteinyldopas. Biochim Biophys Acta 843:49-57