Modification of a Small β‐Barrel Protein,To Give Pseudo‐Amyloid Structures,Inhibits Amyloid β‐Peptide Aggregation

Aggregation of amyloid β‐peptide (Aβ) is closely related to the pathogenesis of Alzheimer’s disease (AD). Although much effort has been devoted to the construction of molecules that inhibit the aggregation of Aβ1‐42, high doses are needed for the inhibition of Aβ aggregation in many cases. Previously, we reported that designed green fluorescent protein (GFP) analogues that gives pseudo‐Aβ β‐sheet structures can work as an aggregation inhibitor against Aβ. To further test this design strategy, we constructed protein analogues that mimic Aβ β‐sheet structures of amyloids by using insulin‐like growth factor 2 receptor domain 11 (IGF2R‐d11) as a scaffold. A designed protein, named IG11KK, which has a parallel configuration of Aβ‐like β sheets, can bind more preferentially to oligomeric Aβ1‐42 than the monomer. Moreover, IG11KK suppressed the aggregation of Aβ1‐42 efficiently, even though lower concentrations of IG11KK than Aβ were used. The aggregation kinetics of Aβ in the presence of the designed proteins revealed that IG11KK can work as an inhibitor not only for the early to middle stages, but also in the latter stage of Aβ aggregation owing to its favorable binding to oligomeric structures of Aβ. The design strategy using β‐barrel proteins such as IGF2R‐d11 and GFP is useful in generating excellent inhibitors of protein misfolding and amyloid formation.     

A novel acylated quercetin tetraglycoside from oolong tea (Camelia sinensis) extracts

A novel acylated quercetin tetraglycoside, namely quercetin 3-O-(2^G-p-coumaroyl-3^G-O-β-l-arabinosyl-3^R-O-β-d-glucosylrutinoside) was isolated from oolong tea (Camelia sinensis) extracts. Structural analysis of this compound was achieved by NMR, TOF-MS and high-resolution FAB-MS. Triglycosyl flavonols have previously been reported from tea leaves and tea seeds however this is the first report of an aromatic acylated and tetraglycosyl flavonol.     

Platinum-catalyzed highly selective thiocarbonylation of acetylenes with thiols and carbon monoxide

A novel carbonylative addition of thiols (RSH) to terminal acetylenes (R′-CCH) takes place successfully in the presence of platinum catalysts under the pressure of carbon monoxide, providing α,β-unsaturated thioesters (R′-C(C(O)SR)CH₂) in good yields regioselectively. This ‘hydrothiocarbonylation’ reaction of acetylenes may include the formation of the platinum sulfide complex as key species.     

Nonfibrous beta-structured aggregation of an Abeta model peptide (Ad-2alpha) on GM1/DPPC mixed monolayer surfaces

Adsorption and aggregation of transformed peptides and proteins onto the cell membrane surface is commonly associated with forms of amyloidosis such as Alzheimer's disease and prion disease. To address dynamic features of these pathological phenomena molecularly, the in situ Ad-2alpha model peptide deposition on glycolipid-containing monolayers was studied by using a 9 MHz quartz-crystal microbalance (QCM). The Ad-2alpha peptide has two amphiphilic alpha-helix segments, each modified with a 1-adamantanecarbonyl group at the N-terminal as a hydrophobic defect. The peptide folds in a 2alpha-helix structure in the bulk solution. In the presence of mixed monolayers of glycolipids (GM1, asialo-GM1, GM3, or LacCer) and/or dipalmitoyl phosphatidylcholine (DPPC) laminated on the QCM plate, the peptide deposition and the conformational change to beta-structure on the monolayers were accelerated. The adsorption kinetics and the amount of Ad-2alpha were dependent on the sort and contents of the glycolipid in the DPPC matrix. Although the Ad-2alpha peptide adsorbs onto most of the glycolipid membranes as monolayer coverage, it adsorbed largely onto the GM1/DPPC (30/70 mol%) mixed monolayer with characteristic kinetic behaviors. The accumulation of beta-structured nonfibrous aggregations was confirmed by AFM and fluorescence microscopy with Thioflavin T (ThT).     

Temperature dependence of Knight shifts for 12 B in Pt

The Knight shift of a short lived β-emitting nucleus ¹²B (I = 1, T _1/2 = 20 ms) implanted into Pt has been measured as a function of temperature (140?600 K) by means of the β-NMR method. The relation between the Knight shift and the susceptibility for Pt was deduced, which shows the similar tendency to that for the case of ¹²B in Pd.     

Polarization of 23Ne, 24m,25Al and 28P produced through single nucleon pickup and charge-exchange reactions at 100 AMeV

We measured the polarization of the $\upbeta $ -emitting ²³Ne (I ^π ?= 5/2^?+?, T _1/2?= 37.24 s) and ²⁵Al(I ^π ?= 5/2^?+?, T _1/2?= 7.18 s) produced through the one nucleon pickup reactions and ^24mAl(I ^π ?= 1^?+?, T _1/2?= 131 ms, E _ex?= 426 keV) and ²⁸P(I ^π ?= 3^?+?, T _1/2?= 270 ms) produced through charge-exchange reactions in the intermediate energy heavy ion collisions. We compared them with those from the projectile fragmentation process. The larger polarization seems to persistently be positive throughout the momentum distribution, and sharper momentum distributions suggest that nuclear friction mechanism is responsible for the polarization phenomena.     

Time-resolved Mössbauer spectra obtained after 57Mn implantation in Si

A new detector system for the coincidence technique between Mössbauer γ-rays and energetic β-rays originating from ⁵⁷Mn has been developed for in-beam Mössbauer spectroscopy using ⁵⁷Mn implantation. This system enables time-resolved Mössbauer measurements of ⁵⁷Fe at various elapsed times after β ^?-decay of ⁵⁷Mn with sufficient quality. We applied this system to the time-dependent measurement of the site distributions of dilute Fe atoms in n-type Si. It was suggested that Fe atoms were already located at substitutional and interstitial positions in Si within a time of about 100 ns after the β ^?-decay of ⁵⁷Mn, and that the occupancy ratio between these positions was hardly dependent on the elapsed time after the β ^?-decay.     

Nuclear structure of proton-rich unstable nucleus 28P studied by g-factor measurement*

Nuclear structure of proton-rich unstable nucleus 28P has been studied by measuring its g-factor for the first time. The g-factor of 28P (Iπ =3+, T1/2=270.3 ms) was measured by means of β-NMR technique combined with the new polarization technique for charge exchange reaction product in the intermediate energy heavy ion collisions. The obtained g-factor of g=0.1028(27) is very much quenched from the Schmidt value,but is well reproduced by the shell model (+0.102). In connection with the magnetic moment of the mirror partner and the β-ray transition probability, the orbital angular momenta and intrinsic spins of protons and neutrons have been determined as 〈lp〉 = 0.43(29), 〈ln〉 = 1.85(29), 〈Sp〉 = 0.28(4), and 〈Sn〉 = 0.44(4).     

Synthesis of a 9-acridinyl nonapeptide containing the DNA recognizing region of 434 phage repressor protein

A peptide-intercalator conjugate was synthesized by connecting acridine with a Gln-Gln-Ser-Ile-Glu-Gln-Leu-Glu-Asn sequence representing the DNA recognizing region of 434 phage repressor protein. This conjugate 7 binds to DNA in spite of its anionic character with the aid of the intercalator.