35661-38-2Relevant articles and documents
COMPOUND FOR PREPARATION OF ANTIBODY-PAYLOAD CONJUGATE AND USE THEREOF
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, (2022/03/15)
The present application relates to a novel linker for use in bioconjugation, comprising two or more electrophilic carbon atoms of a carbonyl group, and a click chemistry functional group and, more specifically, to a linker through which a compound, a peptide, and/or a protein can be directly and/or indirectly linked by a substitution reaction to a desired target molecule, that is, a target molecule.
Mechanistic insight into metal ion-catalyzed transamination
Mayer, Robert J.,Kaur, Harpreet,Rauscher, Sophia A.,Moran, Joseph
supporting information, p. 19099 - 19111 (2021/11/22)
Several classes of biological reactions that are mediated by an enzyme and a co-factor can occur, to a slower extent, not only without the enzyme but even without the co-factor, under catalysis by metal ions. This observation has led to the proposal that metabolic pathways progressively evolved from using inorganic catalysts to using organocatalysts of increasing complexity. Transamination, the biological process by which ammonia is transferred between amino acids and α-keto acids, has a mechanism that has been well studied under enzyme/co-factor catalysis and under co-factor catalysis, but the metal ion-catalyzed variant was generally studied mostly at high temperatures (70-100 °C), and the details of its mechanism remained unclear. Here, we investigate which metal ions catalyze transamination under conditions relevant to biology (pH 7, 20-50 °C) and study the mechanism in detail. Cu2+, Ni2+, Co2+, and V5+ were identified as the most active metal ions under these constraints. Kinetic, stereochemical, and computational studies illuminate the mechanism of the reaction. Cu2+ and Co2+ are found to predominantly speed up the reaction by stabilizing a key imine intermediate. V5+ is found to accelerate the reaction by increasing the acidity of the bound imine. Ni2+ is found to do both to a limited extent. These results show that direct metal ion-catalyzed amino group transfer is highly favored even in the absence of co-factors or protein catalysts under biologically compatible reaction conditions.
Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
, p. 1080 - 1090 (2020/05/25)
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
Determination of Chemical and Enantiomeric Purity of α-Amino Acids and their Methyl Esters as N-Fluorenylmethoxycarbonyl Derivatives Using Amylose-derived Chiral Stationary Phases
Islam, Md. Fokhrul,Adhikari, Suraj,Paik, Man-Jeong,Lee, Wonjae
, p. 332 - 338 (2019/04/13)
Liquid chromatographic enantiomer separation and simultaneous determination of chemical and enantiomeric purity of α-amino acids and their methyl esters as N-fluorenylmethoxycarbonyl (FMOC) derivatives was performed on three covalently bonded type chiral stationary phases (CSPs) derived from amylose derivatives. The enantiomer separation of α-amino acid esters as N-FMOC derivatives was better than that of the corresponding acids, especially for CSP 1 and 2. Chemical impurities as the corresponding racemic acids present in several commercially available racemic amino acid methyl esters were observed to be 0.49–17.50%. Enantiomeric impurities of several commercially available L-amino acid methyl esters were found to be 0.03–0.58%, whereas chemical impurities as the corresponding racemic acids present in the same analytes were found to be 0.13–13.62%. This developed analytical method will be useful for the determination of chemical and enantiomeric purity of α-amino acids and/or esters as N-FMOC derivatives using amylose-derived CSPs.
Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
, p. 4994 - 5002 (2018/10/17)
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors
Narita, Koichi,Matsuhara, Keisuke,Itoh, Jun,Akiyama, Yui,Dan, Singo,Yamori, Takao,Ito, Akihiro,Yoshida, Minoru,Katoh, Tadashi
, p. 592 - 609 (2016/07/06)
Novel C4- and C7-modified FK228 analogues were efficiently synthesized in a highly convergent and unified manner. This synthesis features the amide condensation of glycine-d-cysteine-containing segments with d-valine-containing segments for the direct assembly of the corresponding seco-acids, which are key precursors of macrolactones. The HDAC inhibition assay and cell-growth inhibition analysis of the synthesized analogues revealed novel aspects of their structure-activity relationship. This study demonstrated that simple modification at the C4 and C7 side chains in FK228 is effective for improving both HDAC inhibitory activity and isoform selectivity; moreover, potent and highly isoform-selective class I HDAC1 inhibitors were identified.
The first ratiometric fluorescent probes for aminopeptidase N cell imaging
Chen, Laizhong,Sun, Wei,Li, Jing,Liu, Zhenzhen,Ma, Zhao,Zhang, Wei,Du, Lupei,Xu, Wenfang,Fang, Hao,Li, Minyong
supporting information, p. 378 - 382 (2013/02/23)
In the current paper, three activity-based colorimetric and ratiometric fluorescent probes based on a naphthalimide fluorophore were well designed and synthesized, which can be recognized and hydrolyzed by aminopeptidase N (APN) at both the enzymatic and cellular level by following the fluorescent emission wavelength change from blue to green light. As a result, these molecules were successfully identified as the first ratiometric fluorescent probes for APN cell imaging.
Reversible hydrogen transfer between cysteine thiyl radical and glycine and alanine in model peptides: Covalent H/D exchange, radical-radical reactions, and l - To D -Ala conversion
Mozziconacci, Olivier,Kerwin, Bruce A.,Sch?neich, Christian
experimental part, p. 6751 - 6762 (2011/01/03)
The reversible intramolecular hydrogen transfer reaction of peptide Cys thiyl radicals with Gly and Ala residues was studied in model peptides, where thiyl radicals were either generated through photochemical cleavage of disulfide bonds or through the rea
Total synthesis of (+)-azinothricin and (+)-kettapeptin
Hale, Karl J.,Manaviazar, Soraya,George, Jonathan H.,Walters, Marcus A.,Dalby, Stephen M.
supporting information; experimental part, p. 733 - 736 (2009/09/30)
(Chemical Equation Presented) Asymmetric total syntheses of (+)-azinothricin and (+)-kettapeptin have been completed through a common new pathway that exploits a highly chemoselective coupling reaction between the fully elaborated cyclodepsipeptide 5 and the glycal activated esters 3 and 4 at the final stages of both respective syntheses.
Useful reagents for introduction of Boc and Fmoc protective groups to amines: Boc-DMT and Fmoc-DMT
Hioki, Kazuhito,Kinugasa, Mizuho,Kishimoto, Michiko,Fujiwara, Miho,Tani, Shohei,Kunishima, Munetaka
, p. 1931 - 1933 (2007/10/03)
New amino-protecting reagents, Boc-DMT and Fmoc-DMT, were prepared, and found to be useful for the introduction of Boc and Fmoc groups into amines. Both the reagents can protect various amines including amino acids in good yield in aqueous media. Since the reagents are neither unstable nor irritating, they are practically useful. Georg Thieme Verlag Stuttgart.
