G-quadruplex is a four-stranded G-rich DNA structure that is highly susceptible to oxidation. Despite the important roles that G-quadruplexes play in telomere biology and gene transcription, neither the impact of guanine lesions on the stability of quadruplexes nor their repair are well understood. Here, we show that the oxidized guanine lesions 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydan...

The researches on D-hydantoinase activity and substrate specificity towards dihydropyrimidine and hydantoin derivatives have been carried out intensively over the last few decades. So far, the major efforts have focused on (R,S)-5-phenylhydantoin and (R,S)-5-(4-hydroxyphenyl)hydantoin, the most desirable D-hydantoinase substrates from pharmaceutical industry point of view. However, it was shown...

Hydantoin derivatives, including phenytoin (5,5-diphenylhydantoin), have recently gained attention as they possess a variety of important biochemical and pharmacological properties. Nevertheless, available information on anticancer activity of hydantoin derivatives is still scarce. Here, we evaluated possible antileukemic potential of four phenytoin analogs, namely: methyl 2-(2,4-dioxo-5,5-diph...

A number of structurally related hydantoins has been examined for their effects on the metabolic activities of Ehrlieh aseites carcinoma cells. 5-Ethylsulfinylmethylhydantoin [ESH] was a potent inhibitor of such activities. 5-Ethylsulfonylmethylhydantoin had less activity, and the other hydantoins tested were without effect. ESH was also a potent inhibitor of metabolism in Salk "altered" monkey...

Cisplatin is one of the most successful compounds in the fight against cancer. Recently, interest was directed towards the development of cisplatin analogues which possess Nheterocyclic carrier ligands, coordinated to the cytotoxic platinum(II) moiety, instead of one or both of the am(m)ines. Hydantoins form a large group of derivatives widely applied in medicine and pharmacy, especially as ant...

A number of structurally related hydantoins has been examined for their effects on the metabolic activities of Ehrlieh aseites carcinoma cells. 5-Ethylsulfinylmethylhydantoin [ESH] was a potent inhibitor of such activities. 5-Ethylsulfonylmethylhydantoin had less activity, and the other hydantoins tested were without effect. ESH was also a potent inhibitor of metabolism in Salk "altered" monkey...

Thermostable enzymes find wide applications to basic studies concerning protein stability as well as to development of industrial and specialty bioprocesses. In the process for the production of optically pure D-amino acids, obtained from the corresponding hydantoin derivatives using a microbial D-hydantoinase,1 limited substrate solubility and enzyme stability were posed as problems. In this c...

DNA base-damage recognition in the base excision repair (BER) is a process operating on a wide variety of alkylated, oxidized and degraded bases. DNA glycosylases are the key enzymes which initiate the BER pathway by recognizing and excising the base damages guiding the damaged DNA through repair synthesis. We report here biochemical and structural evidence for the irreversible entrapment of DN...