ARCaDia: single-round screening of a DNA-type targeted covalent binder possessing a latent warhead.

A covalent binder for a target protein was obtained by a direct single-round screening of a latent-warhead-modified DNA library affinity/reactivity-based co-selection of aptameric deoxyribonucleic acid (ARCaDia), followed by a top -mer analysis. The optimal position of the conjugated warhead on the selected aptamer was simultaneously identified.

Atomic structure of the Se-passivated GaAs(001) surface revisited.

We present a combined experimental and theoretical study of the Se-treated GaAs(001)-([Formula: see text]) surface. The ([Formula: see text]) structure with the two-fold coordinated Se atom at the outermost layer and the three-fold coordinated Se atom at the third layer was found to be energetically stable and agrees well with the experimental data from scanning tunneling microscopy, low energy electron diffraction, and x-ray photoelectron spectroscopy. This atomic geometry accounts for the improved stability of the Se-treated surface against the oxidation.

Solvatochromic peptidic binder obtained via extended phage display acts as a fluororeporter for fragment-based drug discovery (FBDD).

We have previously established a selection system to obtain a solvatochromic protein binder from a peptidic fluoroprobe library via the extended T7 phage display. Here, we use the peptidic binder as a fluororeporter in this proof-of-concept study of fragment-based screening approach to drug discovery. The binder is released from the target protein on mixing with an appropriate lead compound, thereby altering its fluorescence color/intensity under 365 nm ultraviolet wavelength irradiation.

Size Optimization of a N-Doped Graphene Nanocluster for the Oxygen Reduction Reaction.

N-Doped graphene nanoclusters (N-GNCs) are promising electrocatalysts for the oxygen reduction reaction (ORR) at the cathode of fuel cells. In this study, the dependence of the ORR activity on the size of N-GNCs was investigated using first-principles calculations based on density functional theory. The maximum electrode potential ( ) was estimated from the free energy of the reaction intermediates of the ORR.

High Accuracy Heartbeat Detection from CW-Doppler Radar Using Singular Value Decomposition and Matched Filter.

Heart rate measurement using a continuous wave Doppler radar sensor (CW-DRS) has been applied to cases where non-contact detection is required, such as the monitoring of vital signs in home healthcare. However, as a CW-DRS measures the speed of movement of the chest surface, which comprises cardiac and respiratory signals by body motion, extracting cardiac information from the superimposed signal is difficult. Therefore, it is challenging to extract cardiac information from superimposed signals.

Direct screening of a target-specific covalent binder: stringent regulation of warhead reactivity in a matchmaking environment.

A peptide-type covalent binder for a target protein was obtained by direct and stringent screening of a warhead-modified peptide library on the robust T7 phage. The aryl fluorosulfate (fosylate) warhead was activated only in a matchmaking microenvironment created between the target protein and an appropriate peptide during the reactivity/affinity-based co-selection process of extended phage display.

Inhibition of thrombin activity by a covalent-binding aptamer and reversal by the complementary strand antidote.

Alleviating the potential risk of irreversible adverse drug effects has been an important and challenging issue for the development of covalent drugs. Here we created a DNA-aptamer-type covalent drug by introducing a sulfonyl fluoride warhead at appropriate positions of the thrombin binding aptamer to create weaponized covalent drugs. We showed the de-activation of thrombin by the novel modality, followed by its re-activation by the complementary strand antidote at an arbitrary time.

Ultrafast spectroscopy on water-processable PCBM: rod-coil block copolymer nanoparticles.

Using ultrafast spectroscopy, we investigate the photophysics of water-processable nanoparticles composed of a block copolymer electron donor and a fullerene derivative electron acceptor. The block copolymers are based on a poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] rod, which is covalently linked with 2 or 100 hydrophilic coil units. In both samples the photogenerated excitons in the blend nanoparticles migrate in tens of ps to a donor/acceptor interface to be separated into free charges.

A medium-firm drug-candidate library of cryptand-like structures on T7 phage: design and selection of a strong binder for Hsp90.

We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 109 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (KD = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD).

Edge-State-Induced Stacking of Zigzag Graphene Nanoribbons.

We have investigated the structural stabilities and electronic properties for AA and the Bernal-stacked AB bilayer zigzag graphene nanoribbons (ZZGNRs) using first-principles calculations within density functional theory. The AB-stacked ZZGNR exhibits the spin-polarized state, while the AA-stacked ZZGNR has the nonmagnetic ground state, being more energetically stable than the AB-stacked one. For the AA-stacked ZZGNR, the interaction between the so-called edge states rather than the van der Waals (vdW) interaction plays an important role: the occupied up-spin and the unoccupied down-spin states at one end of ZZGNR interact with each other, and vice versa at the other end, forming the non-spin-polarized bonding and antibonding states at the zigzag edge.

Effect of Water on the Manifestation of the Reaction Selectivity of Nitrogen-Doped Graphene Nanoclusters toward Oxygen Reduction Reaction.

We investigated the selectivity of N-doped graphene nanoclusters (N-GNCs) toward the oxygen reduction reaction (ORR) using first-principles calculations within the density functional theory. The results show that the maximum electrode potentials ( ) for the four-electron (4e) pathway are higher than those for the two-electron (2e) pathway at almost all of the reaction sites. Thus, the N-GNCs exhibit high selectivity for the 4e pathway, that is, the 4e reduction proceeds preferentially over the 2e reduction.

Facile and Efficient Chemoenzymatic Semisynthesis of Fc-Fusion Compounds for Half-Life Extension of Pharmaceutical Components.

The formation of Fc-fusions, in which biologically active molecules and the Fc fragment of antibodies are linked to each other, is one of the most efficient and successful half-life extension technologies to be developed and applied to peptide and protein pharmaceuticals thus far. Fc-fusion compounds are generally produced by recombinant methods. However, these cannot be applied to artificial middle molecules, such as peptides with non-natural amino acids, unnatural cyclic peptides, or pharmaceutical oligonucleotides.

Micro-Hall Sensors Based on Two-Dimensional Molybdenum Diselenide.

Sensors and electronic devices based on semiconductors in their two-dimensional forms have many advantages. In this paper, we studied micro-Hall sensors based on two-dimensional molybdenum diselenide for the first time. The micro-Hall sensor based on a Ti/MoSe₂/Ti structure clearly showed a linear dependence of the Hall voltage as a function of the magnetic field, with a magnetic sensitivity of ∼16 V/AT.

Fluorescent "keep-on" type pharmacophore obtained from dynamic combinatorial library of Schiff bases.

We established a novel principle for fluorescence detection of a target protein. A low-molecular-weight fluorescent pharmacophore, as a targeted probe, was selected from a dynamic combinatorial library of Schiff bases. The pharmacophore retains its fluorescence when bound to the hydrophobic site of the target, whereas it loses it because of hydrolysis when unbound.

Combinatorially Screened Peptide as Targeted Covalent Binder: Alteration of Bait-Conjugated Peptide to Reactive Modifier.

A peptide-type covalent binder for a target protein was obtained by combinatorial screening of fluoroprobe-conjugated peptide libraries on bacteriophage T7. The solvatochromic fluoroprobe works as a bait during the affinity selection process of phage display. To obtain the targeted covalent binder, the bait in the selected consensus peptide was altered into a reactive warhead possessing a sulfonyl fluoride.

Atomic structure and passivated nature of the Se-treated GaAs(111)B surface.

We have systematically studied the atomic structure and electronic properties of the Se-treated GaAs(111)B surface using scanning tunneling microscopy, reflection high-energy electron diffraction, x-ray photoelectron spectroscopy, and first-principles calculations. We have found that Se atoms substitute [Formula: see text] monolayer of As atoms at the outermost layer of the ideal (111)B surface. Charge transfer from Se to As eliminates all of unsaturated dangling bonds, so that the surface is electronically stabilized, leaving no surface states in the mid-gap region.

Formation of Water Layers on Graphene Surfaces.

Although graphitic materials were thought to be hydrophobic, recent experimental results based on contact angle measurements show that the hydrophobicity of graphitic surfaces stems from airborne contamination of hydrocarbons. This leads us to question whether a pristine graphitic surface is indeed hydrophobic. To investigate the water wettability of graphitic surfaces, we use molecular dynamics simulations of water molecules on the surface of a single graphene layer at room temperature.

Vertical profile of atmospheric conductivity that matches Schumann resonance observations.

We introduce the vertical profile of atmospheric conductivity in the range from 2 to 98 km. The propagation constant of extremely low frequency (ELF) radio waves was computed for this profile by using the full wave solution. A high correspondence is demonstrated of the data thus obtained to the conventional standard heuristic model of ELF propagation constant derived from the Schumann resonance records performed all over the world.

Selection of Color-Changing and Intensity-Increasing Fluorogenic Probe as Protein-Specific Indicator Obtained via the 10BASE(d)-T.

To obtain a molecular probe for specific protein detection, we have synthesized fluorogenic probe library of vast diversity on bacteriophage T7 via the gp10 based-thioetherificaion (10BASE(d)-T). A remarkable color-changing and turning-on probe was selected from the library, and its physicochemical properties upon target-specific binding were obtained. Combination analyses of fluorescence emission titration, isothermal titration calorimetry (ITC), and quantitative saturation-transfer difference (STD) NMR measurements, followed by in silico docking simulation, rationalized the most plausible geometry of the ligand-protein interaction.

Construction of a crown ether-like supramolecular library by conjugation of genetically-encoded peptide linkers displayed on bacteriophage T7.

By using the 10BASEd-T, we have synthesized a crown ether-like macrocyclic library possessing randomized peptide linkers on bacteriophage T7. Among 1.5 × 10(9) diversities of the supramolecule candidates, we have obtained a specific binder for the N-terminal domain of Hsp90.

Pharmacophore generation from a drug-like core molecule surrounded by a library peptide via the 10BASEd-T on bacteriophage T7.

We have achieved site-specific conjugation of several haloacetamide derivatives into designated cysteines on bacteriophage T7-displayed peptides, which are fused to T7 capsid protein gp10. This easiest gp10 based-thioetherification (10BASEd-T) undergoes almost quantitatively like a click reaction without side reaction or loss of phage infectivity. The post-translational modification yield, as well as the site-specificity, is quantitatively analyzed by a fluorescent densitometric analysis after gel electrophoresis.

Gp10 based-thioetherification (10BASE(d)-T) on a displaying library peptide of bacteriophage T7.

The site-specific introduction of a haloacetamide derivative into a designated cysteine on a displaying peptide on a capsid protein (gp10) of bacteriophage T7 has been achieved. This easiest gp10-based thioetherification (10BASEd-T) is carried out in one-pot without side reactions or loss of phage infectivity.

Kinetic analysis of the leucyl/phenylalanyl-tRNA-protein transferase with acceptor peptides possessing different N-terminal penultimate residues.

The introduction of non-natural amino acids at the N-terminus of peptides/proteins using leucyl/phenylalanyl-tRNA-protein transferase (L/F-transferase) is a useful technique for protein engineering. To accelerate the chemoenzymatic reaction, here we systematically optimized the N-terminal penultimate residue of the acceptor peptide. Positively charged, small, or hydrophilic amino acids at this position show positive effects for the reaction.