Kinetics of the formation and structure of oligoperoxide nanolayers and grafted polymer brushes on glass plate surface

Functional oligoperoxide surfactants and coordinating oligoperoxide metal complexes were studied as modifiers of glass flat plates to provide the localization of radical forming sites and other functional fragments in adsorbed polymeric layers of a nanoscale thickness. Both the kinetics of the coating formation and properties of the nanolayers witness the dependence of the packing density of oligoperoxide molecules in the coatings on the oligoperoxide natures, concentrations and conditions of the sorption modification. The availability of definite amount of peroxide groups in formed nanolayer provides the possibility of controlled radical graft polymerization initiated from modified surface leading to reliable surface protection, functionality and targeted surface hydrophilic-hydrophobic properties.      

Design,Synthesis, Evaluation and Structure of Allenic 1α,25-Dihydroxyvitamin D3 Analogs with Locked Mobility at C-17

Vitamin D receptor ligands have potential for the treatment of hyperproliferative diseases and disorders related to the immune system. However, hypercalcemic effects limit their therapeutical uses and call for the development of tissue-selective new analogs. We have designed and synthesized the first examples of 1α,25-dihydroxyvitamin D₃ analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd⁰-mediated cyclization/Suzuki-Miyaura cross-coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester-Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22S)-1α,25-dihydroxy-17,20-dien-24-homo-21-nor-vitamin D₃ bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity.     

Synthesis of γ-halogenated and long-chain β-hydroxy-α-amino acids and 2-amino-1,3-diols using threonine aldolases

The l- and d-threonine aldolase catalyzed formation of γ-halogenated and long-chain l- and d-3-alkylserine-derivatives 1-12, respectively, was shown starting from glycine and halogenated C₂- or C₄-C₁₂ aldehydes. lTA from Pseudomonas putida accepted all tested aldehydes with strongly varying diastereoselectivity (de up to 93%). Only aldehydes smaller than decanal were converted by dTA from Alcaligenes xylosoxidans with good selectivities (de up to 73%). Utilizing isobutanal enantio- and diastereopure d-syn-2-amino-3-hydroxy-4-methylpentanoic acid was obtained (ee>99%, de>95%), which was converted to the corresponding 2-amino-1,3-diol.     

Hydroxy and Methoxy Substituted Thiacarbocyanines for Fluorescent Detection of Amyloid Formations

In present paper series of trimethine cyanines modified in 5,5′- or 6,6′- position with hydroxy- or methoxy- substituents is studied for their ability to interact selectively with fibrillar formations. Processes of dye aggregation that accompany this interaction were also investigated. Meso-methyl trimethynecyanines with 5,5′- methoxy (7519) and hydroxy (7515) substituents strongly (up to 40 times) increase fluorescence intensity in the presence of fibrillar insulin, and also give noticeable fluorescent response on the presence of various aggregated proteins (lysozyme, β-lactoglobulin, α-synuclein A53T). 7519 and 7515 dyes can be used for fluorometric detection of fibrillar insulin at concentrations of approximately 1.5–120 microg/ml. For meso-ethyl substituted dye 7514 the ability to form H- and J-aggregates upon interaction with insulin fibrils was suggested. The model of the H- and J-aggregate packing in the protein fibrillar structure has been proposed.     

Fluorescence Investigation of Interactions Between Novel Benzanthrone Dyes and Lysozyme Amyloid Fibrils

A series of novel fluorescent benzanthrone dyes have been tested for their ability to identify and characterize fibrillar aggregates of lysozyme prepared by protein denaturation in concentrated ethanol solution (F_eth) or acidic buffer (F_ac). Quantitative parameters of the dye association with native and fibrillar protein have been derived from the results of fluorimetric titration. The binding characteristics proved to be different for F_eth- and F_ac-bound benzanthrones, highlighting the dye sensitivity to the distinctions in fibril morphology. By comparing the dye preference to fibrillar protein aggregates, AM2, A8 and A6 were selected as the most prospective amyloid tracers. Based on the analysis of red edge excitation shifts and fluorescence lifetimes of the amyloid-bound dyes it was assumed that surface grooves or dry “steric zipper” interface are potential fibril binding sites for the novel fluorophores.