In and out of the minor groove: Interaction of an AT-rich DNA with the drug CD27

The DNA of several pathogens is very rich in AT base pairs. Typical examples include the malaria parasite Plasmodium falciparum and the causative agents of trichomoniasis and trypanosomiases. This fact has prompted studies of drugs which interact with the minor groove of DNA, some of which are used in medical practice. Previous studies have been performed almost exclusively with the AATT sequence. New features should be uncovered through the study of different DNA sequences. In this paper, the crystal structure of the complex of the DNA duplex d(AAAATTTT)2 with the dicationic drug 4,4'-bis(imidazolinylamino) diphenylamine (CD27) is presented. The drug binds to the minor groove of DNA as expected, but it shows two new features that have not previously been described: (i) the drugs protrude from the DNA and interact with neighbouring molecules, so that they may act as cross-linking agents, and (ii) the drugs completely cover the whole minor groove of DNA and displace bound water. Thus, they may prevent the access to DNA of proteins such as AT-hook proteins. These features are also expected for other minor-groove binding drugs when associated with all-AT DNA. These findings allow a better understanding of this family of compounds and will help in the development of new, more effective drugs. New data on the biological interaction of CD27 with the causative agent of trichomoniasis, Trichomonas vaginalis, are also reported.Postprint (published version

Increased P wave duration in patients with depression or anxiety disorder

Kocer, Abdulkadir/0000-0003-2866-555X; Alcelik, Aytekin/0000-0002-3156-1076WOS: 000277425100011BACKGROUND: Activation of the sympathetic nervous system plays an important role in regulating cardiovascular actions. P wave parameters can provide general information on central cardiovascular autonomic regulatory responses, which are altered in patients with anxiety disorders and depression. In particular, there are no reports addressing changes in P wave duration and dispersion. OBJECTIVE: To compare the differences in P wave duration and P wave dispersion between patients with anxiety disorders and depression, because patients with anxiety disorders and depression develop abnormal electrocardiograms. DESIGN, TIME AND SETTING: A non-randomized concurrent controlled study was performed. Patients with depression and general anxiety disorders were admitted at the psychiatry outpatient clinics of the Medical Faculty of Duzce University of Turkey between May 2005 and October 2006. PARTICIPANTS: A total of 71 consecutive patients with depression and anxiety disorders, as well as 50 physically and mentally healthy age-and gender-matched controls were selected. METHODS: Electrocardiogram records were obtained at the time of admission to the outpatient clinics. MAIN OUTCOME MEASURES: P wave duration and P wave dispersion were measured. RESULTS: Both the maximum (P-max) and minimum (P-min) P wave duration were greater in patients with psychiatric disorders than in healthy controls. P-max was significantly greater in patients with depression or anxiety disorders (Bonferroni test, P 0.017). P waves were similar between panic patients and other anxiety patients. Beck depression results were positively correlated with P-min and P-max (r = 0.374, 0.302, P = 0.013, 0.049, respectively), and not associated with P wave dispersion (P > 0.05). CONCLUSION: Psychiatric disorders are associated with increases in P-max, but not with P wave dispersion. The P wave changes were associated with the degree of depression

In and out of the minor groove: Interaction of an AT-rich DNA with the drug CD27

The DNA of several pathogens is very rich in AT base pairs. Typical examples include the malaria parasite Plasmodium falciparum and the causative agents of trichomoniasis and trypanosomiases. This fact has prompted studies of drugs which interact with the minor groove of DNA, some of which are used in medical practice. Previous studies have been performed almost exclusively with the AATT sequence. New features should be uncovered through the study of different DNA sequences. In this paper, the crystal structure of the complex of the DNA duplex d(AAAATTTT)2 with the dicationic drug 4,4'-bis(imidazolinylamino) diphenylamine (CD27) is presented. The drug binds to the minor groove of DNA as expected, but it shows two new features that have not previously been described: (i) the drugs protrude from the DNA and interact with neighbouring molecules, so that they may act as cross-linking agents, and (ii) the drugs completely cover the whole minor groove of DNA and displace bound water. Thus, they may prevent the access to DNA of proteins such as AT-hook proteins. These features are also expected for other minor-groove binding drugs when associated with all-AT DNA. These findings allow a better understanding of this family of compounds and will help in the development of new, more effective drugs. New data on the biological interaction of CD27 with the causative agent of trichomoniasis, Trichomonas vaginalis, are also reported