ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells

ATP-sensitiveK⁺(K_ATP) channels are therapeutictargets for several diseases, including angina, hypertension, anddiabetes. This is because stimulation ofK_ATP channels is thought toproduce vasorelaxation and myocardial protection against ischemia,whereas inhibition facilitates insulin secretion. It is well known that native K_ATP channels are inhibitedby ATP and sulfonylurea (SU) compounds and stimulated by nucleotidediphosphates and K⁺channel-opening drugs (KCOs). Although these characteristics can beshared with K_ATP channels indifferent tissues, differences in properties among pancreatic, cardiac,and vascular smooth muscle (VSM) cells do exist in terms of the actionsproduced by such regulators. Recent molecular biology andelectrophysiological studies have provided useful information towardthe better understanding of K_ATPchannels. For example, native K_ATPchannels appear to be a complex of a regulatory protein containing theSU-binding site [sulfonylurea receptor (SUR)] and aninward-rectifying K⁺ channel(K_ir) serving as a pore-formingsubunit. Three isoforms of SUR (SUR1, SUR2A, and SUR2B) have beencloned and found to have two nucleotide-binding folds (NBFs). It seemsthat these NBFs play an essential role in conferring the MgADP and KCOsensitivity to the channel, whereas theK_ir channel subunit itselfpossesses the ATP-sensing mechanism as an intrinsic property. Themolecular structure of K_ATPchannels is thought to be a heteromultimeric (tetrameric) assembly ofthese complexes: K_ir6.2 with SUR1(SUR1/K_ir6.2, pancreatic type),K_ir6.2 with SUR2A(SUR2A/K_ir6.2, cardiac type), andK_ir6.1 with SUR2B(SUR2B/K_ir6.1, VSM type)[i.e.,(SUR/K_ir6.x)₄]. It remains to be determined what are the molecular connections betweenthe SUR and K_ir subunits thatenable this unique complex to work as a functionalK_ATP channel.

     

A designed glycopeptide array for characterization of sugar-binding proteins toward a glycopeptide chip technology

For the realization of a practical high-throughput protein detection and analysis system, a novel peptide array has been constructed using a designed glycopeptide model library with an α-helical secondary structure. This study will contribute the increment of the diversity of such an array system and the application to focused proteomics and ligand screening by effective detection of sugar-binding proteins. Fluorescent glycopeptides with an α-helix, a β-strand, or a loop structure were designed initially to select a suitable scaffold for the detection of a model protein. After selection of the α-helical structure as the best scaffold, a small model library with various saccharides was constructed to have charge and hydrophobicity variations in the peptide sequences. When various sugar-binding proteins were added to the peptide library array, the fluorescent peptides showed different responses in fluorescence intensities depending on their sequences as well as saccharides. The patterns of these responses could be regarded as “protein fingerprints” (PFPs), which are able to establish the identities of the target proteins. The resulting PFPs reflected the recognition properties of the proteins. Furthermore, statistical data analysis from obtained PFPs was performed using a cluster analysis. The PFPs of sugar-binding proteins were clustered successfully depending on their families and binding properties. These studies demonstrate that arrays with glycopeptide libraries based on designed structures can be promising tools to detect and analyze the target proteins. Designed peptides with functional groups such as sugars will play roles as the capturing agents of high-throughput protein nano/micro arrays for focused proteomics and ligand screening studies.     

Untersuchungen mit nichtwässerigen Flüssigkeiten

Ohne Zusammenfassung     

Zur physikalischen Chemie der histologischen Färbung

Ohne ZusammenfassungDieses Studium wurde bereits im Jahre 1926 auf Anregung von Herrn Prof. v. Möllendorff in seinem Institut in Kiel aufgenommen, dem der Verfasser an dieser Stelle für damals gewährten freundlichen Rat und Unterstützung bestens danken möchte.     

2′,4′-BNA NC : A Novel Bridged Nucleic Acid Analogue with Excellent Hybridizing and Nuclease Resistance Profiles

Oligonucleotides modified with 2 ′,4 ′-BNA ^NC (N-H)/(N-Me) monomers exhibited excellent hybridizing and nuclease resistance properties. Duplex and triplex thermal stabilities were greatly enhanced by incorporating 2′,4′-BNA ^NC (N-H) and (N-Me) monomers and nuclease resistance was tremendously higher than that of natural oligonucleotide.