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Structural Specificity (structural + specificity)

Distribution by Scientific Domains

Chemistry	60%

Selected Abstracts

DNA Compaction by Divalent Cations: Structural Specificity Revealed by the Potentiality of Designed Quaternary Diammonium Salts

CHEMBIOCHEM, Issue 3 2004
Anatoly A. Zinchenko
Abstract DNA interaction with quaternary diammonium dications, R(CH3)2N+(CH2)nN+(CH3)2R, having various intercharge distances, lengths, and branching, and the chemical nature of the hydrophobic substituents were investigated by fluorescent microscopy and circular dichroism (CD) spectroscopy to reveal their structural specificity for binding to DNA. The conformational behavior of DNA was found to be highly sensitive to the structure of the dications with separated charges. The distance between two ammonium groups greatly influences the compaction activity of the dications. To explain this situation, we proposed a model that demonstrates that the charge density of the dication and the geometric fit between DNA phosphates and the ammonium groups in the dications play an important role in providing efficient DNA collapse. Elongation of the alkyl substituents (R) in the diammonium salts from ethyl to hexyl did not generate any significant alterations in the compaction activities, whereas the branching of substituents caused a drastic decrease in their compaction ability. Based on the results of CD spectroscopy, it was found that the ability of the dications to provoke a DNA transition from the B-form to A-form was also specific: it depended on their intercharge distances and was independent of the length of alkyl substituents. [source]

Identification of a Highly Specific Hydroxyapatite-binding Peptide using Phage Display,

ADVANCED MATERIALS, Issue 10 2008
Marc D. Roy
A peptide sequence SVSVGMKPSPRP that selectively recognizes hydroxyapatite (HA) is identified by using a phage display approach. The engineered sequence exhibits chemical and structural specificity for HA over calcium carbonate and HA's amorphous calcium phosphate precursor. In situ binding to HA in a tooth cross section further demonstrates the sequence specificity and utility in nondestructive imaging applications. [source]

Cold-adapted signal proteins: NMR structures of pheromones from the antarctic ciliate Euplotes nobilii

IUBMB LIFE, Issue 8-9 2007
William J. Placzek
Abstract Cell type-specific signal proteins, known as pheromones, are synthesized by ciliated protozoa in association with their self/nonself mating-type systems, and are utilized to control the vegetative growth and mating stages of their life cycle. In species of the most ubiquitous ciliate, Euplotes, these pheromones form families of structurally homologous molecules, which are constitutively secreted into the extracellular environment, from where they can be isolated in sufficient amounts for chemical characterization. This paper describes the NMR structures of En-1 and En-2, which are members of the cold-adapted pheromone family produced by Euplotes nobilii, a species inhabiting the freezing coastal waters of Antarctica. The structures were determined with the proteins from the natural source, using homonuclear 1H NMR techniques in combination with automated NOESY peak picking and NOE assignment. En-1 and En-2 have highly homologous global folds, which consist of a central three-,-helix bundle with an up-down-up topology and a 310-helical turn near the N-terminus. This fold is stabilized by four disulfide bonds and the helices are connected by bulging loops. Apparent structural specificity resides in the variable C-terminal regions of the pheromones. The NMR structures of En-1 and En-2 provide novel insights into the cold-adaptive modifications that distinguish the E. nobilii pheromone family from the closely related E. raikovi pheromone family isolated from temperate waters. [source]

Blood,brain barrier efflux transport

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2003
Pamela L. Golden
Abstract Efflux transport at the blood,brain barrier (BBB) limits the brain tissue exposure to a variety of potential therapeutic agents, including compounds that are relatively lipophilic and would be predicted to permeate the endothelial lining of the brain microvasculature. Recent advances in molecular and cell biology have led to identification of several specific transport systems at the blood,brain interface. Refinement of classical pharmacokinetic experimentation has allowed assessment of the structural specificity of transporters, the impact of efflux transport on brain tissue exposure, and the potential for drug,drug interactions at the level of BBB efflux transport. The objective of this minireview is to summarize efflux transporter characteristics (location, specificity, and potential inhibition) for transport systems identified in the BBB. A variety of experimental approaches available to ascertain or predict the impact of efflux transport on net brain tissue uptake of substrates also are presented. The potential impact of efflux transport on the pharmacodynamics of agents acting in the central nervous system are illustrated. Finally, general issues regarding the role of identifying efflux transport as part of the drug development process are discussed. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:1739,1753, 2003 [source]