Psoralens and coumarins for receptor targeting on epidermal cells

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:5526716

Jetter, M M

Specific binding sites have been identified for the psoralens, discrete from DNA, in different epidermal cell lines. These receptors are saturable and are alkylated by the action of psoralens + UVA light. A psoralen receptor has been partially purified and established to be a protein of approximately 20,000 daltons. Inhibition of the binding of epidermal growth factor to its receptor and inhibition of the tyrosine kinase activity of the EGF receptor has been associated with PUVA treatment. These findings conflict with the general assumption that the biological effects of psoralens as photoactive compounds are associated with their ability to covalently bind to and crosslink DNA. In collaboration with Laskin's,laboratory, several classes of psoralen agonists were synthesized. These compounds include coumarins, furocoumarin and benzodipyran-2-one derivatives. The methods of preparation were varied and include variants of the Claisen rearrangement, acid and base-catalyzed condensations. The synthesized compounds were tested for their potential inhibition of {sup 125}I-EGF receptor binding. It was discovered that many of these agents showed potent inhibition activity similar to the psoralens. This data offers the possibility that sites of action, other than DNA, are involved in the mechanism by which photoactivated psoralens modulate epidermal cell lines.

• Research Organization: Lehigh Univ., Bethlehem, PA (USA)
• OSTI ID: 5526716
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
560120 -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
CHEMICAL PROPERTIES
COUMARINS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EPIDERMIS
EPITHELIUM
FRACTIONATION
GROWTH FACTORS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MEMBRANE PROTEINS
MITOGENS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PROTEINS
PSORALEN
RADIOISOTOPES
RADIOSENSITIVITY EFFECTS
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
SKIN
TISSUES
TRACER TECHNIQUES