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De novo design of peptide nanoshapes is of great interest in biomolecular science since the local peptide nanoshapes formed by a short peptide chain in the proteins are often key to the biological activities. Here, we show that the de novo design of peptide nanoshapes with sub-nanometer conformational control can be realized using peptides consisting of N-methyl-L-alanine and N-methyl-D-alanine residues as studied by NMR, X-ray and XFEL crystallographic and computational analyses as well as by direct imaging of the dynamics of the peptide’s nanoshape using cinematographic electron microscopic technique. The conformation of N-methyl-L/D-alanine residue is largely fixed because of the restricted bond rotation, and hence can serve as a scaffold on which we can build a peptide into a designed nanoshape. The local shape control by per-residue conformational restriction by torsional strains starkly contrasts with the global shape stabilization of proteins based on many remote interactions. The oligomers allow the bottom-up design of diverse peptide nanoshapes with a small number of amino acid residues and would offer unique opportunities to realize the de novo design of biofunctional molecules, such as catalysts and drugs.

Favipiravir (brand name Avigan), a widely known anti-influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA-dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir-ribofuranosyl-5'-monophosphate (favipiravir-RMP), by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate-determining step in the generation of the active metabolite, quantitative and real-time monitoring of the HGPRT-catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established.

Dissolution-dynamic nuclear polarization (d-DNP) is a state-of-the-art technology that can dramatically enhance the detection sensitivity of nuclear magnetic resonance (NMR). DNP NMR has been applied to small molecules with stable isotopes and has been used to obtain metabolic and physiological information in vivo. However, the hyperpolarized state exponentially decays back to the thermal equilibrium state, depending on the spin-lattice relaxation time (T1). This signal decay has remained a major problem associated with this technology. Therefore, DNP NMR molecular probes useful for in vivo analysis have been limited to naturally occurring small molecules that inherently show long T1. While peptides are promising targets for DNP NMR studies, because of the limitation in T1, DNP NMR molecular probes applicable in vivo have been limited to amino acids or dipeptides. Herein we propose a 13C-labeling strategy to utilize the C-terminal [1-13C]Gly-d2 residue for realizing long T1 in peptides. Structure-based T1 relaxation analysis of amino acids and peptides revealed that (1) T1 does not decrease monotonically with increasing molecular weight and (2) T1 is not significantly affected by a side chain on the neighboring amino acid residue. These findings suggest that the C-terminal [1-13C]Gly-d2 residue affords sufficiently long T1 for biological uses, even in oligopeptides, and allowed us to develop 13C-b- casomorphin-5 (Tyr-Pro-Phe-Pro-[1-13C]Gly-d2, T1 = 24 ± 4 s at 3 T in H2O) and 13C-glutathione (g-Glu-Cys-[1-13C]Gly-d2, T1 = 58 ± 3 s at 3 T in H2O) as DNP NMR probes with long T1. We succeeded in in vivo detection of enzymatic conversions of these two probes. These results demonstrate the utility of our strategy and would contribute to further expansion of the substrate scope for DNP applications.

Dissolution-dynamic nuclear polarization (d-DNP) is a state-of-the-art technology that can dramatically enhance the detection sensitivity of nuclear magnetic resonance (NMR). DNP NMR has been applied to small molecules with stable isotopes and has been used to obtain metabolic and physiological information in vivo. However, the hyperpolarized state exponentially decays back to the thermal equilibrium state, depending on the spin-lattice relaxation time (T1). This signal decay has remained a major problem associated with this technology. Therefore, DNP NMR molecular probes useful for in vivo analysis have been limited to naturally occurring small molecules that inherently show long T1. While peptides are promising targets for DNP NMR studies, because of the limitation in T1, DNP NMR molecular probes applicable in vivo have been limited to amino acids or dipeptides. Herein we propose a 13C-labeling strategy to utilize the C-terminal [1-13C]Gly-d2 residue for realizing long T1 in peptides. Structure-based T1 relaxation analysis of amino acids and peptides revealed that (1) T1 does not decrease monotonically with increasing molecular weight and (2) T1 is not significantly affected by a side chain on the neighboring amino acid residue. These findings suggest that the C-terminal [1-13C]Gly-d2 residue affords sufficiently long T1 for biological uses, even in oligopeptides, and allowed us to develop 13C-β-casomorphin-5 (Tyr-Pro-Phe-Pro-[1-13C]Gly-d2, T1 = 24 ± 4 s at 3 T in H2O) and 13C-glutathione (γ-Glu-Cys-[1-13C]Gly-d2, T1 = 58 ± 3 s at 3 T in H2O) as DNP NMR probes with long T1. We succeeded in in vivo detection of enzymatic conversions of these two probes. These results demonstrate the utility of our strategy and would contribute to further expansion of the substrate scope for DNP applications.

We demonstrate room-temperature 13C hyperpolarization by dynamic nuclear polarization (DNP) using optically polarized triplet electron spins in two polycrystalline systems: pentacene-doped [carboxyl-13C] benzoic acid and microdiamonds containing NV- centers. For both samples, the integrated solid effect (ISE) is used to polarize the 13C spin system in magnetic fields of 350–400 mT. In the benzoic acid sample, the 13C spin polarization is enhanced up to 0.12 % through direct electron-to-13C polarization transfer without performing dynamic 1H polarization followed by 1H-13C cross polarization. In addition, ISE has been successfully applied for the first time to polarize naturally abundant 13C spins in a microdiamond sample to 0.01 %. To characterize the buildup of the 13C polarization, we discuss the efficiencies of direct polarization transfer between the electron and 13C spins as well as that of 13C–13C spin diffusion, examining various parameters which are beneficial or detrimental for successful bulk dynamic 13C polarization.

Distributing entangled photon pairs over noisy channels is an important task for various quantum information protocols. Encoding an entangled state in a decoherence-free subspace (DFS) formed by multiple photons is a promising way to circumvent the phase fluctuations and polarization rotations in optical fibres. Recently, it has been shown that the use of a counter-propagating coherent light as an ancillary photon enables us to faithfully distribute entangled photon with success probability proportional to the transmittance of the optical fibres. Several proof-of-principle experiments have been demonstrated, in which entangled photon pairs from a sender side and the ancillary photon from a receiver side originate from the same laser source. In addition, bulk optics have been used to mimic the noises in optical fibres. Here, we demonstrate a DFS-based entanglement distribution over 1km-optical fibre using DFS formed by using fully independent light sources at the telecom band. In the experiment, we utilize an interference between asynchronous photons from cw-pumped spontaneous parametric down conversion (SPDC) and mode-locked coherent light pulse. After performing spectral and temporal filtering, the SPDC photons and light pulse are spectrally indistinguishable. This property allows us to observe high-visibility interference without performing active synchronization between fully independent sources., 8 pages, 5 figures

We theoretically analyze the performance of the nuclear magnetic resonance (NMR) spectroscopy with a superconducting flux qubit (FQ). Such NMR with the FQ is attractive because of the possibility to detect the relatively small number of nuclear spins in a local region ($\ensuremath{\approx}\ensuremath{\mu}\mathrm{m}$) with low temperatures ($\ensuremath{\approx}\mathrm{mK}$) and low magnetic fields ($\ensuremath{\approx}\mathrm{mT}$), in which other types of quantum sensing schemes cannot easily be accessed. A sample containing nuclear spins is directly attached on the FQ, and the FQ is used as a magnetometer to detect magnetic fields from the nuclear spins. Especially, we consider two types of approaches to NMR with the FQ. One of them is to use spatially inhomogeneous excitations of the nuclear spins, which are induced by a spatially asymmetric driving with radio-frequency (rf) pulses. Such an inhomogeneity causes a change in the dc magnetic flux penetrating a loop of the FQ, which can be detected by a standard Ramsey measurement on the FQ. The other approach is to use a dynamical decoupling on the FQ to measure ac magnetic fields induced by Larmor precession of the nuclear spins. In this case, neither a spin excitation nor a spin polarization is required since the signal comes from fluctuating magnetic fields of the nuclear spins. We calculate the minimum detectable density (number) of the nuclear spins for the FQ with experimentally feasible parameters. We show that the minimum detectable density (number) of the nuclear spins with these approaches is around ${10}^{21}/{\mathrm{cm}}^{3}$ (${10}^{8}$) with an accumulation time of 1 s.

Dissolution dynamic nuclear polarization (DNP) has wide variety of important applications such as real-time monitoring of chemical reactions and metabolic imaging. We construct DNP using photoexcited triplet electron spins (Triplet-DNP) apparatus combined with dissolution apparatus for solution NMR in a high magnetic field. Triplet-DNP enables us to obtain high nuclear polarization at room temperature. Solid-state samples polarized by Triplet-DNP are transferred to a superconducting magnet and dissolved by injecting aqueous solvents. The 13C polarization of 0.22% has been obtained for [caryboxy-13C]benzoic acid-d in the liquid state. Our results show that Triplet-DNP can be applied to real-time monitoring with solution NMR.

A solution with hyperpolarized nuclear spins encoded into a long-lived state has been utilized for sensing chemical phenomena. In a conventional way, nuclear spins are hyperpolarized at very low temperatures. In this work, we demonstrate the encoding of a four-nuclear-spin system hyperpolarized at room temperature into a long-lived state in a solution. We apply the solution with the long-lived state as a sensor in ligand--receptor binding experiments.

Trapped atomic ions are ideal single photon emitters with long lived internal states which can be entangled with emitted photons. Coupling the ion to an optical cavity enables efficient emission of single photons into a single spatial mode and grants control over their temporal shape. These features are key for quantum information processing and quantum communication. However, the photons emitted by these systems are unsuitable for long-distance transmission due to their wavelengths. Here we report the transmission of single photons from a single $^{40}\text{Ca}^{+}$ ion coupled to an optical cavity over a 10 km optical fibre via frequency conversion from 866 nm to the telecom C-band at 1,530 nm. We observe non-classical photon statistics of the direct cavity emission, the converted photons and the 10 km transmitted photons, as well as the preservation of the photons' temporal shape throughout. This telecommunication ready system can be a key component for long-distance quantum communication as well as future cloud quantum computation.

Typically, the aim of quantum metrology is to sense target fields with high precision utilizing quantum properties. Unlike the typical aim, in this paper, we use quantum properties for adding a new functionality to quantum sensors. More concretely, we propose a delegated quantum sensor (a client-server model) with security inbuilt. Suppose that a client wants to measure some target fields with high precision, but he/she does not have any high-precision sensor. This leads the client to delegate the sensing to a remote server who possesses a high-precision sensor. The client gives the server instructions about how to control the sensor. The server lets the sensor interact with the target fields in accordance with the instructions, and then sends the sensing measurement results to the client. In this case, since the server knows the control process and readout results of the sensor, the information of the target fields is available not only for the client but also for the server. We show that, by using an entanglement between the client and the server, an asymmetric information gain is possible so that only the client can obtain the sufficient information of the target fields. In our scheme, the server generates the entanglement between a solid state system (that can interact with the target fields) and a photon, and sends the photon to the client. On the other hand, the client is required to possess linear optics elements only including wave plates, polarizing beam splitters, and single-photon detectors. Our scheme is feasible with the current technology, and our results pave the way for a novel application of quantum metrology., Comment: 15 pages, 10 figures, close to published version