A5012231552- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Sulfur-Based Synthesis Techniques
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Reactions
- Biochemical and Structural Characterization
- Peptidase Inhibition and Analysis
- Chronic Lymphocytic Leukemia Research
- Carbohydrate Chemistry and Synthesis
- Biotin and Related Studies
- Biosimilars and Bioanalytical Methods
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Neuropeptides and Animal Physiology
- Rheumatoid Arthritis Research and Therapies
- Steroid Chemistry and Biochemistry
- Photochromic and Fluorescence Chemistry
- Multicomponent Synthesis of Heterocycles
- Glycosylation and Glycoproteins Research
- Autophagy in Disease and Therapy
- Fluorine in Organic Chemistry
- Sphingolipid Metabolism and Signaling
- Synthesis and Catalytic Reactions
- Receptor Mechanisms and Signaling
- Protein purification and stability
Tokushima University
2014-2025
Institute of Biomedical Science
2020-2024
Tokushima University Hospital
2023
Kyoto University
2018-2021
Kyoto University Hospital
2018-2021
Kyoto Pharmaceutical University
2018-2021
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs) are widely used as antidiabetic and anti-obesity agents. Although conventional GLP-1 RAs such liraglutide semaglutide acylated with fatty acids to delay their degradation by dipeptidylpeptidase-4 (DPP-4), the manufacturing process is challenging. We previously developed selectively lipidated peptides at only tryptophan residue (peptide A having one 8-amino-3,6-dioxaoctanoic acid (miniPEG) linker B three miniPEG linkers). In this...
Monoclonal antibodies have accelerated the availability of treatment options for many diseases in which molecular mechanism has been elucidated detail. Therefore, an assay that can universally analyze clinical pharmacokinetics and cross-sectional studies would be indispensable. We developed a universal antibody bioanalysis with Fab-selective tryptic reaction, named nano-surface molecular-orientation limited (nSMOL) proteolysis, collects specific signature peptides biological samples. Using...
Late-stage formation of a sactionine thioether bond connecting Gly α-carbon and Cys thiol was achieved by Lossen rearrangement glycyl hydroxamic acid (GlyHA) residue in peptide. allowed conversion GlyHA within peptide to an N-acyl iminium equivalent, which subsequently reacted with S-acetamidomethyl (Cys(Acm)) TFA the presence guanidine hydrochloride (Gn·HCl) yield desired linkage final stage.
The ligand-dependent incorporation of a reporter molecule (e.g., fluorescence dye or biotin) onto endogenous target protein has emerged as an important strategy for elucidating function using various affinity-based labelling reagents consisting reporter, ligand and reactive units. Conventional generally use weakly activated unit, which can result in the non-specific proteins ligand-independent manner. In this context, activation reagent through targeted protein-ligand interaction could...
A tyrosine (Tyr)- or tryptophan (Trp)-selective metal-free C-H sulfenylation reaction using an acid-activated S-acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from Cys(Acm)(O) under acidic conditions allows the of Tyr. Significantly, in presence trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys-Tyr-linked peptide even Trp residues. In contrast, Cys-Trp-linked was selectively obtained guanidine...
Lipidation of peptides is a promising means modification that can improve the therapeutic character biologically active peptides. Here, novel lipidation protocol for described. The C–H sulfenylation indole in using S-p-methoxybenzyl cysteine sulfoxide under acidic conditions presence ammonium chloride, anisole, and triisopropylsilane enables late-stage tryptophan-selective peptide lipidation. This developed has been used successfully glucagon-like Oral glucose tolerance tests wild-type mice...
Peptide thioesters are very useful in protein chemistry, and chemistry- biochemistry-based protocols used for the preparation of thioesters. Among such protocols, only a few approaches have been use naturally occurring peptide sequences. The development chemistry-based applicable to natural sequences remains challenge, methods would be major contribution science. Here, we describe using innovative methodology that features nickel(II)-mediated alcoholysis sequence, followed by O-N N-S acyl...
An N-sulfanylethylaminooxybutyramide (SEAoxy) has been developed as a novel thioester equivalent for native chemical ligation. SEAoxy peptide was straightforwardly synthesized by conventional Fmoc solid-phase synthesis without problem. Moreover, could be directly applied to ligation owing the intramolecular N-to-S acyl shift that releases peptide-thioester in situ. This methodology successfully of two bioactive peptides.
Sulfanylmethyl-installed dimethylaminopyridine, 2-sulfanylmethyl-4-dimethylaminopyridine (2), has an acidic thiol group comparable to that in aryl thiols due the formation of a zwitterion consisting thiolate anion and pyridinium cation. It can be used as additive for native chemical ligation. The alkyl 2 allows it one-pot ligation–desulfurization protocol peptide synthesis. utility synthesis cyclic peptides is demonstrated.
An advanced insulin synthesis is presented that utilizes one-pot/stepwise disulfide bond formation enabled by acid-activated S-protected cysteine sulfoxides in the presence of chloride anion. S-chlorocysteine generated from reacts with an to afford S-sulfenylsulfonium cation, which then furnishes or reversely returns starting materials depending on S-protection employed and reaction conditions. Use S-acetamidomethyl (Cys(Acm)) its sulfoxide (Cys(Acm)(O)) selectively give under weak acid...
1,2-Aminothiols operate as an <italic>S</italic>-deprotecting reagent for <italic>S</italic>-Acm cysteine with the aid of CuSO<sub>4</sub> under aerobic conditions.
Abstract Covalent linking of side chains provides a method to produce cyclic or stapled peptides that are important in developing peptide‐based drugs. A variety crosslinking formats contribute fixing the active conformer and prolonging its biological activity under physiological conditions. One format uses cysteine thiol participate through nucleophilic thiolate anions thiyl radicals form thioether disulfide bonds. Removal S‐protection from an S‐protected Cys derivative generates thiol,...
CXCL14 is a primordial CXC-type chemokine that transports CpG oligodeoxynucleotides (ODN) into endosomes and lysosomes in dendritic cells, thereby leading to the activation of Toll-like receptor 9 (TLR9)-mediated innate immune system. However, underlying molecular mechanism by which CXCL14-CpG ODN complex enters cells remains elusive. Herein, we describe chemical synthesis CXCL14-derived photoaffinity probes their application identification target receptors for using quantitative proteomics....
An advanced insulin synthesis is presented that utilizes one-pot/stepwise disulfide bond formation enabled by acid-activated S-protected cysteine sulfoxides in the presence of chloride anion. S-chlorocysteine generated from reacts with an to afford S-sulfenylsulfonium cation, which then furnishes or reversely returns starting materials depending on S-protection employed and reaction conditions. Use S-acetamidomethyl (Cys(Acm)) its sulfoxide (Cys(Acm)(O)) selectively give under weak acid...
An oxidant-free approach to the synthesis of
A traceable linker that is potentially applicable to identification of a target protein bioactive compounds was developed. It enabled not only thiol-induced cleavage the for enrichment but also selective labelling pick out from contaminated non-target proteins facile identification.
Binding pockets of a schizophrenia-related<sc>d</sc>-amino acid oxidase to its inhibitor were clarified by docking simulation and protein labeling experiments.
Infliximab (IFX) therapy has considerably improved the treatment of rheumatoid arthritis (RA). However, some patients still do not respond adequately to IFX therapy, or efficacy diminishes over time. Although previous studies have reported a relationship between serum levels and therapeutic efficacy, potential applications drug monitoring (TDM) in clinical practice remain unclear. The purpose this study was investigate TDM by analyzing Japanese cohort database. Data were collected...