Molecular modelling of the interaction of pentamidine analogues with d(CGCGAATTCGCG)2 duplex.

A molecular mechanics approach has been used to examine the structure of the complexes formed between d(CGCGAATTCGCG)2 duplex and furan-containing analogues of pentamidine (I-II). The resulting structures of the drug-DNA complexes and their energetics have been examined. From the energetic analysis it appears that van der Waals and electrostatic interactions are more important than specific hydrogen bonds in stabilizing the ligand-duplex complexes.

Cytotoxicity and effect on collagen biosynthesis of proline analogue of melphalan as a prolidase-convertible prodrug in cultured human skin fibroblasts.

Proline analogue of melphalan (MEL-PRO) was synthesised as a prodrug susceptible to the action of ubiquitously distributed, cytosolic imidodipeptidase--prolidase [E.C.3.

The suitability of DNA extracted from formalin-fixed, paraffin-embedded tissues for double differential polymerase chain reaction analysis.

Formalin-fixed, paraffin-embedded (FFPE) tissues are one of the popular sources of diagnostic materials, the easiest to store and transport. They are often used as the source of nucleic acids for retrospective molecular analyses based on DNA amplification by polymerase chain reaction (PCR). However, it is known that nucleic acids from paraffin-embedded tissues are much worse templates than those recovered from fresh tissues.

Aromatic extended bisamidines: synthesis, inhibition of topoisomerases, and anticancer cytotoxicity in vitro.

A series of four aromatic extended bisamidines (12-15) differing in the nature of their terminal basic side chains were synthesized and evaluated for cytotoxic activity in MCF-7 cultured breast cancer cells. The concentrations of 12, 13, 14, and 15 needed to inhibit [3H]thymidine incorporation into DNA by 50% (IC50) were found to be 63 microM, 85 microM, 77 microM, and 97 microM, respectively. To test whether cytotoxic properties were related to DNA-binding and topoisomerase action, the bisamidines 12-15 were evaluated in a cell-free system.

Synthesis, molecular modelling, and antiproliferative and cytotoxic effects of carbocyclic derivatives of distamycin with chlorambucil moiety.

New carbocylic analogues of distamycin and netropsin with chlorambucil moieties 5-8 have been synthesised. Data from the ethidium displacement assay showed that these compounds bind in the minor groove of DNA. The observed reduced affinity to AT pairs and increased affinity towards GC sequences of the carbocyclic lexitropsins with chlorambucil moiety 5-8 in comparison with netropsin and distamycin was observed and rationalised by means of molecular modelling techniques.

DNA-binding activity and cytotoxicity of the extended diphenylfuran bisamidines in breast cancer MCF-7 cells.

The DNA binding properties of three novel extended diphenylfuran bisamidines (1-3) possessing different dicationic terminal side chains were studied. The ultrafiltration assay showed that bisamidines 1-3 have significant affinity for DNA. The DNA-binding data for bisamidines 1-3 using homopolymers poly(dA-dT)- poly(dA-dT) and poly(dG-dC)- poly(dG-dC), indicated that these compounds show moderate specificity for AT base pairs.

Decreased cytotoxicity and increased antimitotic activity of a proline analogue of chlorambucil as a prodrug susceptible to the action of fibroblast's prolidase.

We synthesized an proline analogue of chlorambucil (CH-pro) as a prodrug susceptible to the action of ubiquitously distributed, cytosolic imidopeptidase--prolidase [E.C.3.

Molecular modelling of the interaction of carbocyclic analogues of netropsin and distamycin with d(CGCGAATTCGCG)2.

A molecular mechanics and molecular dynamics approach was used to examine the structure of complexes formed between the d(CGCGAATTCGCG)2 duplex and netropsin, distamycin, and four carbocyclic analogues of netropsin and distamycin (1-4). The resulting structures of the ligand-DNA model complexes and their energetics were examined. It is predicted that the compounds 1-4 should have a decreased affinity for the minor groove of AT-rich regions in comparison to netropsin and distamycin.

Prolidase-activated prodrug for cancer chemotherapy cytotoxic activity of proline analogue of chlorambucil in breast cancer MCF-7 cells.

Although prolidase [EC 3.4.13.

HCV infection in Poland.

Background: Hepatitis C virus (HCV) infection is one of the most prevalent infectious diseases in the world. In 1997, hepatitis C became a statutorily noticeable disease in Poland. Nevertheless, to date, only a few notable studies on the prevalence of HCV infection have been carried out in Poland.

Establishment of hairy root cultures of Ammi majus.

Axenically grown Ammi majus plantlets were inoculated with seven different Agrobacterium rhizogenes strains. Hairy root lines were established only after inoculation with the two agropine strains: A4 and LBA9402. The growth rate of hairy root cultures was about thirty times faster than that of callus and cell suspension cultures.

Relationship of c-myc and erbB oncogene family gene aberrations and other selected factors to ex vivo chemosensitivity of ovarian cancer in the modified ATP-chemosensitivity assay.

A pilot study on relationships of selected molecular factors [erbB-1, erbB-2, erbB-3, and c-myc oncogene average gene copy numbers (AGCN); steroid receptors and pS2 gene expression; tumor cells' DNA values] to the ex vivo chemosensitivity of ovarian cancer in a modified adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA), was performed. Despite the relatively small number of patients, numerous correlations among the factors tested were found. Nevertheless, only c-myc gene dosage positively affected ex vivo chemosensitivity of tumors tested.

c-myc oncogene gene dosage, serum CEA and CA-15.3 antigen levels, and cellular DNA values in relation to ex vivo chemosensitivity of primary human breast cancer.

A pilot study on relationships of selected molecular factors (c-myc oncogene average gene copy numbers (AGCN); serum CEA and CA 15.3 antigen levels; tumor cells' DNA values), to the ex vivo chemosensitivity of primary female human breast cancer in a modified adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA), was performed. Four drug combinations were tested.

Inhibitory effects of pentamidine analogues on protein biosynthesis in vitro.

Pentamidine despite its rather high toxicity, is currently in clinical use. For development of new drugs of this type it is important to know the mechanism of their action. Two new amidines (I and II) and 4',6-diamidino-2-phenylindole (DAPI) were found in preliminary experiments to inhibit protein synthesis in vitro in the cell-free rat liver system.

Prolidase as a prodrug converting enzyme. III. Synthesis of proline analogues of melphalan and theirs susceptibility to the action of prolidase.

The feasibility to targeting prolidase as an antineoplastic prodrug-converting enzyme has been examined. The synthesis of proline analogues of melphalan (well known antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. One of the compounds, N-[[[[(S)-carboxy]pyrrolidin-1-yl]carbonyl]methyl]-4-[bis(2-chloro ethyl) amino]-2-phenylalanine, was found as very good prolidase substrate with susceptibility over 2 fold higher compared to standard, endogenous its substrate--Gly-L-Pro.

Identification, characterization and purification of the lantibiotic staphylococcin T, a natural gallidermin variant.

Staphylococcin T (StT), an antibacterial agent produced by a Staphylococcus cohnii T strain, was purified to homogeneity by ammonium sulphate precipitation, gel filtration, cation exchange and fast performance liquid chromatography (FPLC). The final yield was about 20%, and over a 1000-fold increase in the specific activity was obtained. Mass determination (2166 Da), amino acid sequencing (Ile-Ala-Xaa-Lys-Phe-Leu-Xaa-Xaa-Pro-Gly-Xaa-Ala-Lys-block) and DNA sequencing demonstrated that StT is identical to gallidermin, a lanthionine-containing antimicrobial peptide.

[Hemolytic activity of Klebsiella pneumoniae and Klebsiella oxytoca].

We demonstrated that Klebsiella pneumoniae and Klebsiella oxytoca possess a selective haemolytic activity on rabbit erythrocytes. Thirty one Klebsiella strains (18 strains of K. pneumoniae and 13 strains of K.

Prolidase as a prodrug converting enzyme. II. Synthesis of proline analogue of anthraquinone-2-carboxylic acid and its susceptibility to the action of prolidase.

The feasibility to targeting prolidase as an antineoplastic prodrug--converting enzyme has been examined. The synthesis of proline analogue of anthraquinone-2-carboxylic acid (potential antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. The product was found to be insoluble in aqueous solution while in the presence of 1% DMSO complete solubility of the compound was achieved.

Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer.

ErbB-4 protein is a recently discovered member of the ErbB family. The role of ErbB-4 protein in mammary-gland tissue has not been definitively established. To date, the expression of erbB-4 in breast tissue has been determined in only a few cases and, to the best of our knowledge, its amplification has not been examined.

Synthetic analogues of netropsin and distamycin--synthesis of a new pyridine and carbocyclic analogues of the pyrrolecarboxamide antitumour antibiotics.

A new series of pyridine-containing analogues III-XXII of distamycin A and netrop sin was investigated by the molecular mechanics technique and molecular modelling. A pyridine analogue of netropsin (VII) is described, the first compound based on molecular studies, and two carbocyclic analogues of distamycin A with an N-terminal chloro- or bromoacetyl group (VIa, VIIa) were synthesized, as well as carbocyclic analogues of netropsin (VIIIb, Xb), potential carriers of alkylating elements. The potential use of VIa, VII, VIIa, VIIIb and Xb as carriers to place into the minor groove of DNA chemical groups capable of modifying DNA, is discussed.

Prolidase as a prodrug converting enzyme I. Synthesis of proline analogue of chlorambucil and its susceptibility to the action of prolidase.

The feasibility to targeting prolidase as an antineoplastic prodrug-converting enzyme has been examined. The synthesis of proline analogue of chlorambucil (well known antineoplastic agent) conjugated through imido-bond (potential target for prolidase action) has been performed. It was found that the product of synthesis, N-[4-[4-(N,N-bis(2-chloroethyl)amino) phenyl]butyryl]-L-proline is insoluble in aqueous solutions but it may be solubilized in methanol.

Drastically decreased transcription from CII-activated promoters is responsible for impaired lysogenization of the Escherichia coli rpoA341 mutant by bacteriophage lambda.

It was demonstrated previously that a mutation, rpoA341, in the gene encoding the alpha subunit of Escherichia coli RNA polymerase prevents lysogenization by bacteriophage lambda. The rpoA341 allele is known to be responsible for impaired transcription of some positively regulated E. coli chromosomal operons.