Visualized and Quantitative Conformational Analysis of Peptidomimetics.

Protein-protein interactions (PPIs) are fundamentally important and challenging drug targets. Peptidomimetic molecules of various types have been developed to modulate PPIs. A particularly promising drug discovery strategy, structural peptidomimetics, was designed based on special mimicking of side-chain Cα-Cß bonds. It is simple and versatile. Nevertheless, no quantitative method has been established to evaluate its similarity to a target peptide motif. We developed two methods that enable visual, comprehensive, and quantitative analysis of peptidomimetics: peptide conformation distribution (PCD) plot and peptidomimetic analysis (PMA) map. These methods specifically examine multiple side-chain Cα-Cß bonds of a peptide fragment motif and their corresponding bonds (pseudo-Cα-Cß bonds) in a mimetic molecule instead of φ and ψ angles of a single amino acid in the traditional Ramachandran plot. The PCD plot is an alignment-free method, whereas the PMA map is an alignment-based method providing distinctive and complementary analysis. Results obtained from analysis using these two methods indicate our multifacial α-helix mimetic scaffold 12 as an excellent peptidomimetic that can precisely mimic the spatial positioning of side-chain functional groups of α-helix. These methods are useful for visualized and quantified evaluation of peptidomimetics and for the rational design of new mimetic scaffolds.

Silver-Catalyzed C(sp3)-H Chlorination.

A silver-catalyzed chlorination of benzylic, tertiary, and secondary C(sp3)-H bonds was developed. The reaction proceeded with as low as 0.2 mol % catalyst loading at room temperature under air atmosphere with synthetically useful functional group compatibility. The regioselectivity and reactivity tendencies suggest that the chlorination proceeded through a radical pathway, but an intermediate alkylsilver species cannot be ruled out.

Directing activator-assisted regio- and oxidation state-selective aerobic oxidation of secondary C(sp(3))-H bonds in aliphatic alcohols.

The regioselective conversion of an unactivated C(sp(3))-H bond of a methylene carbon (CH2) into a C-O single bond is an attractive reaction in organic synthesis. Herein, we present a strategy for a regio- and oxidation state-selective aerobic C-H oxidation based on an N-hydroxyamide-derived directing activator (DA), which is attached to a hydroxy group in alcohol substrates. The DA reacts with NOx species generated in situ from NaNO2, a Brønsted acid, and aerobic oxygen, and effectively generates an amidoxyl radical from the N-hydroxy moiety of the DA. Then, the amidoxyl radical promotes site-selective intramolecular C-H abstraction from methylenes with γ- (or δ-) selectivity. The thus-generated methylene radicals are trapped by molecular oxygen and NO. This process results in the predominant formation of nitrate esters as products, which suppresses undesired overoxidation. The products can be easily converted into alcohols after hydrogenolysis.

Chemo- and regioselective oxygenation of C(sp3)-H bonds in aliphatic alcohols using a covalently bound directing activator and atmospheric oxygen.

Chemically reactive directing groups (directing activators) represent a promising strategy for mild and regioselective C(sp3)-H functionalization. The use of a radical N-oxyl directing activator promoted the aerobic oxygenation of benzylic, propargylic, tertiary, and unactivated acyclic methylene C(sp3)-H bonds in aliphatic alcohols with γ- (or δ-) selectivity under mild conditions (room temperature to 50 °C). The reaction was unaffected by the presence of various oxidation-sensitive functional groups, which proved to be problematic in previously reported studies on the oxidation of C(sp3)-H bonds. Structural modifications on the directing activator altered the regioselectivity, and thus provided an ultra-remote aerobic C(sp3)-H oxygenation. The observed reactivity and regioselectivity could be rationalized in terms of the intramolecular conformational accessibility of the N-oxyl radical and the electronic characteristics of C(sp3)-H bonds.

Estimation of muscle fatigue by ratio of mean frequency to average rectified value from surface electromyography.

A new method to estimate muscle fatigue quantitatively from surface electromyography (EMG) is proposed. The ratio of mean frequency (MNF) to average rectified value (ARV) is used as the index of muscle fatigue, and muscle fatigue is detected when MNF/ARV falls below a pre-determined or pre-calculated baseline. MNF/ARV gives larger distinction between fatigued muscle and non-fatigued muscle. Experiment results show the effectiveness of our method in estimating muscle fatigue more correctly compared to conventional methods. An early evaluation based on the initial value of MNF/ARV and the subjective time when the subjects start feeling the fatigue also indicates the possibility of calculating baseline from the initial value of MNF/ARV.

Estimation of respiratory signal from thoracic impedance cardiography in low electrical current.

A new method to estimate respiratory signal from thoracic impedance is proposed. To realize battery powered, wearable respiratory monitoring devices, low current impedance measurement techniques are desired. However, under low current conditions, conventional methods to separate cardiac and respiratory signals do not work well as the cardiac signal is much larger than the respiratory signal. In the proposed method, respiratory signal is estimated by calculating an envelope curve from the detected T waves of cardiac component. The results of the experiments show that the accuracy of proposed method is greater than conventional method.

Fixation distance estimation using vergence eye movement for automatic focusing glasses.

In this study, we propose a method for estimating fixation distance on the basis of measurements of vergence eye movements. The aim of this approach is to control the lens focus of automatic focusing glasses. To reduce user effort at the time of calibration, the calibration was performed at infinite distance gazing, and the parameters were determined from the premeasured pupillary distance at infinity and iris diameters. To clarify the effectiveness of the proposed method, we conducted evaluation experiments using prototype glasses. The results showed that even participants requiring myopic correction could perform accurate motion vergence movements. Fixation distance estimation showed that, with the eye calibrated at infinite distance gazing, shorter distances could be estimated with an average accuracy exceeding 90%.

Estimating uncomfortable loudness levels using evoked potentials to auditory stimuli for hearing aid fitting.

Determining the loudest sound level that a person can comfortably tolerate (uncomfortable loudness level: UCL) imposes a strain on people suffering from hearing loss. In the present study, we propose a method of estimating UCL based on auditory evoked potentials (AEPs). Adults with normal hearing (18 men aged 25-56 years) participated in the study. Three tone bursts (S1, S2 and S3; a triplet) of the same frequency (either 1k, 2k or 4k Hz) were presented to the right or left ear with an interstimulus interval of 300 ms. The sound intensity decreased gradually by 5 dB HL from 80 dB (S1) to 70 dB HL (S3). The interval between triplets was 450 ± 50 ms. The frequency of a given triplet differed from the frequency of the preceding triplet. An electroencephalogram was recorded from three scalp electrode sites (Cz, C3, and C4) with the right mastoid reference. The 900-ms period after the onset of the triplet was transformed to a wavelet coefficient and averaged separately by stimulated ear and tone frequency. The UCLs were estimated by linear discriminant analysis on the basis of trained data of the other participants' subjective UCLs and the wavelet coefficients. The mean estimation error was 4.9 ± 5.0 dB. This result suggests that the UCLs could be estimated successfully on the basis of AEPs to triplets of auditory tones.