Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization**

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides. These peptide-EBXs can be readily accessed, by both solution- and solid-phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C-terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein-protein interaction inhibition.     

Acid-Resistant BODIPY Amino Acids for Peptide-Based Fluorescence Imaging of GPR54 Receptors in Pancreatic Islets

The G protein-coupled kisspeptin receptor (GPR54 or KISS1R) is an important mediator in reproduction, metabolism and cancer biology; however, there are limited fluorescent probes or antibodies for direct imaging of these receptors in cells and intact tissues, which can help to interrogate their multiple biological roles. Herein, we describe the rational design and characterization of a new acid-resistant BODIPY-based amino acid (Trp-BODIPY PLUS), and its implementation for solid-phase synthesis of fluorescent bioactive peptides. Trp-BODIPY PLUS retains the binding capabilities of both short linear and cyclic peptides and displays notable turn-on fluorescence emission upon target binding for wash-free imaging. Finally, we employed Trp-BODIPY PLUS to prepare some of the first fluorogenic kisspeptin-based probes and visualized the expression and localization of GPR54 receptors in human cells and in whole mouse pancreatic islets by fluorescence imaging.     

两类手性PNA单体及其对映异构体的合成

分别以保护的Ｌ－和Ｄ－赖氨酸作为起始原料合成了两种类型的ＰＮＡ单体。在类型Ｉ中，碱基通过－ＣＨ２Ｃ（Ｏ）－间隔臂与赖氨酸的α－ＮＨ相连，而类型Ⅱ中，－Ｃ（Ｏ）－用作连接臂。     

Electrochemical Activation of CO2 for the Synthesis of Ethyl Carbanilate under Mild Conditions

A novel electrochemical procedure for the synthesis of ethyl carbanilate from aniline and carbon dioxide was developed via the selective cathodic reduction of carbon dioxide in CO2-saturated DMF solution containing 0.1 mol/L TEABr at room temperature,followed by the addition of EtI as an alkylating agent.The synthesis was carried out under mild[p(CO2)=1.0×105 Pa,t=20 ℃] and safe conditions.Influences of the nature of the electrodes,the current densities,the passed charges during electrolysis,temperatures,and supporting electrolytes on the yield of ethyl carbanilate were studied to optimize the electrolytic conditions.The selectivity of ethyl carbanilate is 100%.     

Synthesis of Two New Chiral Blocks for the Construction of Peptide Nucleic Acid (PNA)

AnewtypeofDNAmimictermedPNA(PeptideNtlcleicAcid).wasfirstpreparedbyNielsenela/'intileearly1990s.ItisanoligonucleotideanalogueinwhichtheentiredeoxyribosephosphatebackbonehasbeenreplacedbyachemicallycompletelydilTerent.butstructurallyhomomorphousachira...     

The Electrochemical Oxidation of N,N‐Diethyl‐p‐Phenylenediamine in DMF and Analytical Applications. Part I: Mechanistic Study

The electrochemical oxidation of N,N‐diethyl‐p‐phenylenediamine in dimethylformamide has been studied at platinum and gold microdisk electrodes of various radii between 6.7 and 66 μm. The voltammetric responses revealed two electrochemically reversible waves the second of which becomes larger at higher concentrations and bigger electrode radii. The voltammetric signals have been modelled and the electrochemical oxidation reaction is not inconsistent with an EC_revECE reaction. Kinetic parameters are reported.     

LiFePO_4电化学反应机理、制备及改性研究新进展

作为用于可持续能源的有效能量存储装置,锂离子电池因具有优异的电化学性能而得到广泛研究,是非常有发展潜力的储能电池体系,其技术发展及应用的关键在于电极材料的研发。LiFePO_4作为锂离子电池正极材料之一,具有循环寿命长、能量密度大、充放电平稳、热稳定性良好、安全性好、重量轻和低毒性等优点,备受国内外专家的专注。然而,LiFePO_4正极材料的研究还存在一些技术瓶颈,由于其存在电导率相对较低、锂离子扩散系数小以及振实密度不高等问题,导致循环性能、低温特性和高倍率充放电性能等并不理想,因而制约着它的应用和发展。近几年研究工作者通过改进制备工艺以及进行相关改性研究,旨在逐步解决上述问题。本文简要综述了LiFePO_4正极材料的最新研究成果,就其结构特征、电化学反应机理、制备方法和改性进行了系统介绍。探讨了目前LiFePO_4正极材料面临的主要问题及可能的解决策略,并对其未来的研究方向和应用前景进行了展望。     

Electrochemical ELISA for the screening of DDT related compounds: analysis in waste waters

An electrochemical enzyme-linked immunosorbent assay (ELISA) for the detection of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DTT), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE), 1,1-dichloro-2,2-bis-(4-chlorophenyl)ethane (p,p′-DDD) and o,p-DDT was developed. Optimization of the ELISA competition conditions, led to similar response for the p,p′-isomers. The activity of the label enzyme (horseradish peroxidase) was measured electrochemically using 3,3′,5,5′-tetramethylbenzidine as substrate. The use of purified antiserum for p,p′-DDT resulted in a sensitive assay with a detection limit of 40 pg ml⁻¹ and R.S.D. ranging from 1 to 3% intra-day and 3 to 6% inter-day. No matrix effect for waste water samples of different origin has been evidenced. The ELISA was used to detect DDTs in 20 samples after extraction in diethylether. This method appears suitable for routine screening of DDTs without sample pre-treatment other than dilution in PBS or after organic solvent extraction if high sensitivity is required.     

Intramolecular Hydrogen Bonding Enables a Zwitterionic Mechanism for Macrocyclic Peptide Formation: Computational Mechanistic Studies of CyClick Chemistry

Macrocyclic peptides have become increasingly important in the pharmaceutical industry. We present a detailed computational investigation of the reaction mechanism of the recently developed “CyClick” chemistry to selectively form imidazolidinone cyclic peptides from linear peptide aldehydes, without using catalysts or directing groups (Angew. Chem. Int. Ed. 2019 , 58, 19073–19080). We conducted computational mechanistic to investigate the effects of intramolecular hydrogen bonds (IMHBs) in promoting a kinetically facile zwitterionic mechanism in “CyClick” of pentapeptide aldehyde AFGPA. Our DFT calculations highlighted the importance of IMHB in pre-organization of the resting state, stabilization of the zwitterion intermediate, and the control of the product stereoselectivity. Furthermore, we have also identified that the low ring strain energy promotes the “CyClick” of hexapeptide aldehyde AAGPFA to form a thermodynamically more stable 15+5 imidazolidinone cyclic peptide product. In contrast, large ring strain energy suppresses “CyClick” reactivity of tetra peptide aldehyde AFPA from forming the 9+5 imidazolidinone cyclic peptide product.     

A Convergent Strategy for the Modification of Peptide Nucleic Acids: Novel Mismatch-Specific PNA-Hybridization Probes

Coupling of nonnatural nucleobases to the orthogonally protected backbone 1 on the solid phase provided access to novel peptide nucleic acid (PNA) conjugates 2 , which are difficult to synthesize by standard routes. Hybridization probes containing the thiazolorange dye might allow DNA sequence analysis in real time. B−CH₂CO=modified nucleobase, fluorescent dye, etc; Boc, Fmoc=protecting groups.     

Supramolecular Binding with Lectins: A New Route for Non-Covalent Functionalization of Polysaccharide Matrices

The chemical functionalization of polysaccharides to obtain functional materials has been of great interest in the last decades. This traditional synthetic approach has drawbacks, such as changing the crystallinity of the material or altering its morphology or texture. These modifications are crucial when a biogenic matrix is exploited for its hierarchical structure. In this work, the use of lectins and carbohydrate-binding proteins as supramolecular linkers for polysaccharide functionalization is proposed. As proof of concept, a deproteinized squid pen, a hierarchically-organized β-chitin matrix, was functionalized using a dye (FITC) labeled lectin; the lectin used was the wheat germ agglutinin (WGA). It has been observed that the binding of this functionalized protein homogenously introduces a new property (fluorescence) into the β-chitin matrix without altering its crystallographic and hierarchical structure. The supramolecular functionalization of polysaccharides with protein/lectin molecules opens up new routes for the chemical modification of polysaccharides. This novel approach can be of interest in various scientific fields, overcoming the synthetic limits that have hitherto hindered the technological exploitation of polysaccharides-based materials.     

Low Cost Layer by Layer Construction of CNT/Chitosan Flexible Paper‐based Electrodes: A Versatile Electrochemical Platform for Point of Care and Point of Need Testing

Modification of cellulosic paper with carbon nanotubes (CNT) was studied for the development of electronic and analytical devices. Interesting results were published by using a CNT aqueous solution and the capillary forces of filter paper to make conductive tracks, supercapacitors, potentiometric electrodes and chemometric sensors. In this report, we show for the first time an electrochemical characterization of CNT‐CS‐SDS paper electrodes constructed with an ink containing optimized proportions of multi‐wall CNT, chitosan (CS) and sodium dodecyl sulfate (SDS), and we compared our data with CNT‐SDS paper electrodes constructed with a previously reported ink. We achieved better reversibility (ΔE=131±14 mV, CVs) and reproducibility (RSD=3.63 %) with CNT‐CS‐SDS paper electrodes, when compared to CNT‐SDS paper electrodes (ΔE=249±7 mV; RSD=6.8 %) used as controls. When electrodes were fold at 90° angle, CNT‐CS‐SDS paper electrodes showed lower RSD than CNT‐SDS paper electrodes, 8.43 % and 21.5 % respectively. These results are in concordance with SEM analysis indicating a dense CS film in CNT‐CS‐SDS paper electrodes. As a proof of concept, we determine dopamine concentration by DPV in the presence of ascorbic and uric acids, the limit of detection calculated was 6.32 μM. Moreover, a bismuth‐film was prepared by in situ plating of Bi into CNT‐CS‐SDS paper electrodes. ASV allowed us to detect Pb in the presence of Bi (10–200 ppb) with a limit of detection of 6.74 ppb.     

New PEPTIR-2.0 Peptide Designed for Use as Recognition Element in Electrochemical Biosensors with Improved Specificity towards E. coli O157:H7

The detection of pathogens through alternative methodologies based on electrochemical biosensors is being studied. These devices exhibit remarkable properties, such as simplicity, specificity, and high sensitivity in monitoring pathogens. However, it is necessary to continue conducting studies that adequately improve these characteristics, especially the recognition molecule. This work aims to design and evaluate a new peptide, named PEPTIR-2.0, as a recognition molecule in electrochemical biosensors to detect E. coli O157:H7 in water. PEPTIR-2.0 was obtained from modifications of the PEPTIR-1.0 peptide sequence, which was previously reported and exhibited excellent properties for detecting and quantifying this pathogenic microorganism. PEPTIR-1.0 is a peptide analogous to the TIR (Translocated Intimin Receptor) protein capable of interacting with the Intimin outer membrane. The basis of this study was to obtain, by using bioinformatics tools, a molecule analogous to PEPTIR-1.0 that maintains its three-dimensional structure but increases the hydrophobic interactions between it and Intimin, since these intermolecular forces are the predominant ones. The designed PEPTIR-2.0 peptide was immobilized on screen-printed electrodes modified with gold nanoparticles. The detection capacity of E. coli O157:H7 in water was evaluated using electrochemical impedance spectroscopy in the presence of other microorganisms, such as P. aeruginosa, S. aureus, and non-pathogenic E. coli. The results showed that PEPTIR-2.0 confers remarkable specificity to the biosensor towards detecting E. coli, even higher than PEPTIR-1.0.     

Incorporation of biotinylated manganese-salen complexes into streptavidin: New artificial metalloenzymes for enantioselective sulfoxidation

Incorporation of achiral biotinylated manganese-salen complexes into streptavidin yields artificial metalloenzymes for aqueous sulfoxidation using hydrogen peroxide. Four biotinylated salen ligands were synthesized and their manganese complexes were tested in combination with several streptavidin mutants, yielding moderate conversions (up to 56%) and low enantioselectivities (maximum of 13% ee) for the sulfoxidation of thioanisole.     

Quinaldinium Chlorochromate Supported on Alumina: A New and Efficient Reagent for the Oxidation of Alcohols

Summary. The new, mild chromium(VI) oxidizing agent, quinaldinium chlorochromate supported on neutral alumina, was prepared as a stable yellow solid. The reagent is suitable to oxidize various primary and secondary alcohols to the corresponding carbonyl compounds and anthracene to anthraquinone in good yields.     

Radial Electrochemical Flow Cell for On‐Line Coupling with Mass Spectrometry: Theory and Electrooxidation of Dimethylaminomethyl Ferrocene

A new, radial, miniature, three‐electrode flow cell is introduced. The cell's configuration is most suitable for on‐line electrochemistry – mass spectrometry since it is characterized by low resistive losses, high conversion efficiency, and isolation of the counter electrode reaction by‐products from the product stream reaching the MS. A mathematical model describing convection diffusion in the radial cell is developed. Cell's performance can be predicted over a wide parametric range by a simple mathematical expression which converges to the Levich equation under low conversion conditions. The performance of the cell is demonstrated by studies of dimethylaminomethyl ferrocene (DMAMF) oxidation which is a simple single electron charge transfer reaction and allows validation of the mathematical model. The theoretical predictions of the model were in agreement with the results of on‐line electrochemistry – mass spectrometry studies of DMAMF.