Search

Abstract: The μ-conotoxin KIIIA is a three disulfide-bridged blocker of voltage-gated sodium channels (VGSCs). The Lys7 residue in KIIIA is an attractive target for manipulating the selectivity and efficacy of this peptide. Here, we report the design and chemical synthesis of μ-conopeptoid analogues (peptomers) in which we replaced Lys7 with peptoid monomers of increasing side-chain size: N-methylglycine, N-butylglycine and N-octylglycine. In the first series of analogues, the peptide core contained all three disulfide bridges; whereas in the second series, a disulfide-depleted selenoconopeptide core was used to simplify oxidative folding. The analogues were tested for functional activity in blocking the Nav1.2 subtype of mammalian VGSCs exogenously expressed in Xenopus oocytes. All six analogues were active, with the N-methylglycine analogue, [Sar7]KIIIA, the most potent in blocking the channels while favouring lower efficacy. Our findings demonstrate that the use of N-substituted Gly residues in conotoxins show promise as a tool to optimize their pharmacological properties as potential analgesic drug leads. [Copyright &y& Elsevier]

• In this work, we study a ferroelectric liquid crystal (FLC) cell as a phase-only modulator. The novelty of the approach is the use of a FLC cell with a large switching rotation angle close to 90° instead of the typical value used in display applications, which is less than 45 ∘. • We show that when the LC layer is a half-wave retarder, this device provides a binary π phase modulation for any input state of polarization and with maximum light conversion efficiency, thus being useful even for unpolarized light. This situation is not possible with the common nematic LC modulators or with standard FLC modulators of smaller rotation angles. • The main physico-chemical properties of the liquid crystalline mixture used to fabricate the FLC modulator are studied. In addition, we perform a reverse engineering procedure aimed at verifying the modulator's physical parameters and the binary π -phase modulation. In this work a ferroelectric liquid crystal (FLC) modulator with a non-standard large switching rotation angle, close to 90 ∘ , is fabricated and characterized. The modulator acts as a switchable wave-plate with an in-plane rotation of the principal axis under the action of a bipolar voltage. In the ideal situation of half-wave retardance, the device is shown to behave as a binary π phase modulator independently of the input state of polarization. We provide physico-chemical properties of the liquid crystalline mixture used to fabricate the FLC modulator with such large switching angle. The characterization method of the device optical properties is presented, which allows the localization of the two LC stable states, the unambiguous determination of the rotation angle, and the evaluation of the spectral retardance function. We demonstrate the polarization-independent π phase shift using an adapted Young's type interferometer for real-time measurements, where we further analyze the operational frequency limits of the device. This FLC operational mode can be exploited to produce binary-phase polarization-independent diffractive optical elements. [ABSTRACT FROM AUTHOR]

Abstract: Five serine proteinase inhibitors (Mirabilis jalapa trypsin inhibitors, MJTI I and II and Spinacia oleracea trypsin inhibitors, SOTI I, II, and III) from the garden four-o’clock (M. jalapa) and spinach (S. oleracea) seeds were isolated. The purification procedures included affinity chromatography on immobilized methylchymotrypsin in the presence of 5M NaCl, ion exchange chromatography and/or preparative electrophoresis, and finally RP–HPLC on a C-18 column. The inhibitors, crosslinked by three disulfide bridges, are built of 35 to 37 amino-acid residues. Their primary structures differ from those of known trypsin inhibitors, but showed significant similarity to the antimicrobial peptides isolated from the seeds of M. jalapa (MJ-AMP1, MJ-AMP2), Mesembryanthemum crystallinum (AMP1), and Phytolacca americana (AMP-2 and PAFP-S) and from the hemolymph of Acrocinus longimanus (Alo-1, 2 and 3). The association equilibrium constants (K a) with bovine β-trypsin for the inhibitors from M. jalapa (MJTI I and II) and S. oleracea (SOTI I–III) were found to be about 107 M−1. Fully active MJTI I and SOTI I were obtained by solid-phase peptide synthesis. The disulfide bridge pattern in both inhibitors (Cys1–Cys4, Cys2–Cys5 and Cys3–Cys6) was established after their digestion with thermolysin and proteinase K followed by the MALDI-TOF analysis. [Copyright &y& Elsevier]