Binding of chromomycin A3 (CRA) to calf thymus DNA was investigated in the presence of divalent cations using visible absorption and 1H-nmr spectroscopies. An apparent equilibrium binding constant (approximately 10(11) M-1) was obtained from metal competition experiments using EDTA to remove the metal cation from the DNA-M-CRA (M: metal) complex. The large binding constant of the drug to DNA enabled us to obtain essentially complete complexation of CRA to the short homogeneous d(ATGCAT)2 duplex using stoichiometric amounts of the metal cation. Large induced chemical shifts were observed in the 1H-nmr spectrum of the above complex using the paramagnetic Co2+ cation, indicating that the metal occupies a unique binding site. Since no induced 1H-nmr chemical shifts were observed for the drug-Co2+ mixture, it was concluded that no metal-drug complex is formed. In addition, it was found that bound CRA is negatively charged at physiological pH and binding to the DNA could be affected only by using metal cations whose ionic radius size (less than 0.85 A) and charge (2+) were simultaneously satisfied. Stringent metal cation selectivity for the DNA-M-CRA complex may be intimately connected with the antitumor selectivity of CRA, since different types of cells generally possess widely differing molar concentrations of metal cations.

Purpose of Review In the setting of kidney transplantation, the ureter is a common source for complications. As a result, prevention of ureteral complications and their management is of crucial importance. In this context, the purpose of this review is to summarize recent literature on the ureter in the kidney transplant setting with a special focus on new findings. We conducted a PubMed and Medline search over the last 10 years to identify all new publications related to ureteroneoimplantations, stents and management of complications in the kidney transplant setting. Recent Findings Performance of the "Lich-Gregoir" technique for ureteroneocystostomy seems to be favourable in regard to postoperative complications when compared with other methods described in the literature. Moreover, major urologic complications can be further reduced by ureteral stenting. Summary A new approach for management of ureteral strictures in renal transplants is presented. We discussed the usage of a ureteral stent covered with a biostable polymer aiming to prevent tissue ingrowth into the lumen as a new option for management of ureteral stricture in the kidney transplant setting.

SynopsisThe interactions of the antitumor antibiotics, chromomycin A,, with a variety of metal cations in the pH range of 3.0-8.5 were systematically studied by CD, absorption, and 'H-nmr spectroscopies. Results were compared with thaw obtained in the presence of increasing amounts of calf thymus DNA. The negatively charged chromomycin A,, pK, 6.3, forms aggregates that become ordered and smaller in size, in the presence of variety of metal cations. Spectrophotometric titrations have shown that binding of the neutral drug to DNA at pH 4.5 does not require divalent cations, although the strength of the binding is greatly enhanced in their presence. At higher pH values ( > 7.0) and low DNA/drug ratio (< 20), the metal cations are necessary to induce the binding between chromomycin A, and DNA. At higher DNA/drug ratios (> 100 : I), an appreciable proportion of the drug is bound even in the absence of divalent cations. Its binding affinity to the DNA is enhanced in the presence of these cations and at low pH values. Therefore, we conclude that chromomycin A, binds to DNA in two related modes, in the presence and in the absence of divalent cations. The spectral data accumulated indicate the metal cation is involved in the binding of the drug to the DNA by forming a drug-metal-DNA ternary complex.