Comparison Of The Structure And Energies Of Psoralen Dna Adducts

A series of six nitroxide spin-labeled psoralens were designed, synthesized and tested as probes for DNA dynamics. The synthesis of these spin-labeled psoralen derivatives and their photoreactivity with double-stranded DNA fragments is described. The spin labels (nitroxides) were demonstrated to survive the uv irradiation required to bind the probe to the target DNA. EPR spectra of the photobound spin-labels indicate that they do not wobble with respect to the DNA on the time-scales investigated. The author has used psoralen modified DNA as a model for the study of DNA repair enzyme systems in human cell free extracts. He has shown that damage-induced DNA synthesis is associated with removal of psoralen adducts and therefore is {open_quotes}repair synthesis{close_quotes} and not an aberrant DNA synthesis reaction potentiated by deformation of the DNA by adducts. He has found that all DNA synthesis induced by psoralen monoadducts is the consequence of removal of these adducts. By the same approach he has obtained evidence that this in vitro system is capable of removing psoralen cross-links as well. Reported here are synthetic methods that make use of high intensity lasers coupled with HPLC purification to make homogeneous and very pure micromole quantities of furan-side monoadducted, cross-linked, and pyrone-side monoadducted DNA oligonucleotide. These molecules are currently being studied by NMR and X-ray crystallography. The application of the site-specifically psoralen modified oligonucleotide synthesized by these methods to the construction of substrates for the investigation of DNA repair is also discussed.

In one form or another psoralens have been in use dating back to biblical times for the treatment of depigmented patches of skin. However, it has only been in the past 40 years that the structure and function of psoralens have been elucidated. Although several volumes have been published on photobiology and photomedicine, no one volume has ever been devoted to the psoralen photobiology. In these two volumes we focus on the properties and uses of photoactivated psoralens.In these volumes the various aspects of psoralens are presented in a review of the field as it stands in mid 1986. In retrospect, we may find that this particular time was crucial in the development of new therapeutic modalities as many of the applications of modem molecular biology are beginning to impact on the practice of medicine.This book was written with two purposes in mind. First, to serve as an update (the last collective review of the field was in 1982). Second, it is hoped that newcomers to the fields of photobiology andphotomedicine both scientists and clinicians would find it a useful introduction.

Over the years, researchers have reported solubility data in the chemical, pharmaceutical, engineering, and environmental literature for several thousand organic compounds. Until the first publication of the Handbook of Aqueous Solubility Data, this information had been scattered throughout numerous sources. Now newly revised, the second edition of

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