Separation and identification of platinum adducts with DNA nucleotides by capillary zone electrophoresis and capillary zone electrophoresis coupled to mass spectrometry.

Platinum adducts are supposed to be the cytotoxic lesions in DNA after platinum-containing anticancer therapy. Various adducts are formed upon interaction of platinum complexes with nucleotides, but contribution of individual adducts to antitumor activity and toxicity of platinum complexes still remains to be examined. A capillary zone electrophoresis (CZE) method is described that is suitable to separate individual platinum adducts. We investigated the formation of adducts following the reaction of cis-diamminedichloroplatinum (II) (cisplatin) with various DNA nucleotides. Baseline separation of unmodified and modified nucleotides (adducts) was achieved using uncoated fused-silica capillaries and basic separation buffers. In order to elucidate the observed peak pattern, a coupled CZE-electrospray ionization-mass spectrometry (ESI)-MS approach was applied. After incubation of mononucleotides with cisplatin, monochloro, monoaqua and bifunctional adduct species were detected. Consequently, the migration order of nucleotides and individual platinum adducts could be determined. Moreover, the time-dependent conversion from monochloro to monoaqua and subsequently to bifunctional adducts was monitored. In conclusion, individual platinum adducts were separated by CZE and identified by CZE-ESI-MS. Formation and conversion of distinct species were confirmed. Potential applications comprise studies of novel platinum complexes, investigations of platinum-adduct formation with DNA, and determination of platinum-DNA adducts in cells.

[Optimization of capillary electrophoretic separation of more nucleotide base acids]. / Optimierung kapillarelektrophoretischer Trennungen mehrbasischer Säuren.

Capillary electrophoresis is a useful tool for the analysis of nucleotides. Their charge depends on the pH of the buffer system used. An equation is developed for calculation the partial charge of acids with more than one dissociation constant in dependence on the pH and the ionic strength of the buffer. There is no limitation to the number of dissociation constants. The partial charges and from these the relative mobility according to Offord were calculated for 4 nucleotid-monophosphates. They agree very well with the experimental electrophoretic data.

[Incontinentia pigmenti as the leading symptom]. / Incontinentia pigmenti als Leitsymptom.

It is reported on four girls aged 8 to 20 with Incontinentia pigmenti (Ip) The ectodermal dysplasia was associated with oligophrenia, therapy resistant epilepsy with severe psychorganic syndromes and dementia, Lennox syndrome, lability of emotion with severe disorders of social adaptations, spasticity, hypo- and areflexia, hemiathetosis, choreiform unrest, pathological EEG findings, including spike-potentials; relations to cleidocranial dysostosis, dysraphia, Poland's, Greig's and Chotzen's syndrome were found. Ip means unfavourable prognosis and progression of neuropsychiatric disorders.