'DNA snapback' peptides

Thermal denaturation studies show that 10-15% of the calf thymus DNA in the heat denatured (Tyr-Gly-Tyr-Gly-Tyr)-DNA complex renatures spontaneously after colling. The double-strandness of this DNA was verified by its resistance to single-strand Neurospora endonuclease and by its elution profile on hydroxypatite columns. The renatured DNA isolated by the latter technique was found to contain 56% GC compared to the 41% GC content of the whole thymus DNA. Alternating tryptophanyl-glycyl and histidyl-glycyl peptides also catalyze the same renaturation. A linear correlation was found between the thermal stabilization afforded to the DNA by the various peptides and their ability to "catalyze" DNA strand renaturation.     

Three-Dimensional Self-Gravito-Acoustic Solitary Waves in a Degenerate Quantum Plasma System

Plasma Physics Reports - Three-dimensional self-gravito-acoustic solitary waves (SGASWs) in a general (but realistic) self-gravitating degenerate quantum plasma media consisting of heavy...     

Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase

Six AChE monooxime-monocarbamoyl reactivators with an (E)-but-2-ene linker were synthesized using modification of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and insecticide paraoxon was tested in vitro. The reactivation efficacies of pralidoxime, HI-6, obidoxime, K048, K075 and the newly prepared reactivators were compared. According to the results obtained, one reactivator seems to be promising against tabun-inhibited AChE and two reactivators against paraoxon-inhibited AChE. The best results were obtained for bisquaternary substances with at least one oxime group in position four.     

Non-polar solutes in water and in aqueous solutions of protein denaturants. Modeling of solution and transfer processes

A simple molecular model for the thermodynamic behavior of non-polar solutes in water and in aqueous solutions of protein denaturants is presented. Three contributions are considered: (i) combinatorial arising from the mixing process, (ii) interactional characterizing the molecular interactions occurring in the mixture and (iii) a contribution originating from the structural changes occurring in the first shell of water molecules around the solute. The latter is modeled assuming that water molecules in contact with the solute are involved in a chemical equilibrium between two states. The model describes well the temperature and denaturant concentration dependences of the Gibbs energies of solution and transfer for benzene, toluene and alkanes in water and aqueous solutions of urea and guanidine hydrochloride. Model parameters are physically meaningful, allowing a discussion of the molecular interactions involved. A preferential solvation of the solute by the denaturant is found. However, the non-polar solute-denaturant interaction is not specific, i.e. leading to a distinct chemical entity. Urea and guanidine hydrochloride are non-polar solubilizing agents because their interactions with the solute are less unfavorable than those between water and the solute.     

Investigating the antiproliferative activity of quinoline-5,8-diones and styrylquinolinecarboxylic acids on tumor cell lines

The structure-activity relationships of new quinoline based compounds were investigated. Quinoline-5,8-dione and styrylquinoline scaffolds were used for the design of potentially active compounds. The novel analogues had comparable antiproliferative activity to cisplatin when evaluated in a bioassay against the P388 leukemia cell line. However, these compounds appeared far less efficient against SK-N-MC neuroepithelioma cells. Analogues without the 5,8-dione structure but containing the 8-carboxylic acid group were also found to induce antiproliferative activity. Hydrophobicity as measured by HPLC did not correlate with antiproliferative activity.     

Inhibition of RNA chain initiation in E. coli core RNA polymerase with 2-hydroxy-5-nitrobenzyl bromide

The modification of $\text{E. coli}$ core RNA polymerase with 2-hydroxy-5-nitrobenzyl bromide (Koshland's Reagent) resulted in the benzylation of 6 out of 13 cysteines, and 10 out of 20 tryptophans in the polymerase, and occurred with an 8% decrease in its [θ]₂₂₀. The modification resulted in a maximal inhibition of 60% of the RNA chains on both calf thymus and micrococcal DNA templates. γ-³²P-ATP studies showed the inhibition occurred at RNA chain initiation. This study raises the possibility that the modified core polymerase may synthesize specific RNA(s).     

Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines

Manufacturing procedures for cellular therapies are continuously improved with particular emphasis on product safety. We previously developed a dendritic cell (DC) cancer vaccine technology platform that uses clinical grade lipopolysaccharide (LPS) and interferon (IFN)-y for the maturation of monocyte derived DCs. DCs are frozen after 6 hrs exposure at a semi-mature stage (smDCs) retaining the capacity to secret interleukin (IL)-12 and thus support cytolytic T-cell responses, which is lost at full maturation. We compared closed systems for monocyte enrichment from leucocyte apheresis products from healthy individuals using plastic adherence, CD14 selection, or CD2/19 depletion with magnetic beads, or counter flow centrifugation (elutriation) using a clinical grade in comparison to a research grade culture medium for the following DC generation. We found that elutriation was superior compared to the other methods showing 36 ± 4% recovery, which was approximately 5-fold higher as the most frequently used adherence protocol (8 ± 1%), and a very good purity (92 ± 5%) of smDCs. Immune phenotype and IL-12 secretion (adherence: 1.4 ± 0.4; selection: 20 ± 0.6; depletion: 1 ±0.5; elutriation: 3.6 ± 1.5 ng/ml) as well as the potency of all DCs to stimulate T cells in an allogeneic mixed leucocyte reaction did not show statistically significant differences. Research grade and clinical grade DC culture media were equally potent and freezing did not impair the functions of smDCs. Finally, we assessed the functional capacity of DC cancer vaccines manufactured for three patients using this optimized procedure thereby demonstrating the feasibility of manufacturing DC cancer vaccines that secret IL-12 (9.4 ± 6.4 ng/ml). We conclude that significant steps were taken here towards clinical grade DC cancer vaccine manufacturing.     

Investigation of new acyloxy derivatives of cholic acid and their esters as drug absorption modifiers

Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. Intestinal absorption promoters/enhancers are used as excipients in oral formulations of poorly oral-bioavailable drugs. Series of fourteen acyloxy derivatives of 5β-cholic acid as potential drug absorption modifiers was generated by multistep synthesis. The synthesis of all newly prepared compounds is presented here. Structure confirmation of all generated compounds was accomplished by (1)H NMR, (13)C NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R(M)) was determined. The hydrophobicity (logP) and solubility (logS) of the studied compounds were also calculated using two commercially available programs. All the target compounds were tested for their in vitro transdermal penetration activity and as potential intestinal absorption enhancers. The anti-proliferative activity of all the final compounds was also assessed against the human cancer cell lines: T-lymphoblastic leukemia cell line and the breast adenocarcinoma cell line. Their cytotoxicity was also evaluated against the normal human skin fibroblast cells. Two compounds showed anti-proliferative effect on cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC(50)>37 μM), indicating they would have low cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effects are discussed in this article.     

Synthesis of a novel series of non-symmetrical bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase

Nine potential non-symmetrical xylene-bridged AChE reactivators were synthesized using modifications of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and the insecticide paraoxon together with nine symmetrical xylene-bridged compounds, was tested in vitro. Seven compounds were promising against paraoxon-inhibited AChE. Two compounds were found to be more potent against tabun-inhibited AChE than obidoxime at a concentration applicable in vivo.