13515-93-0Relevant articles and documents
Oxidative damage of proline residues by nitrate radicals (NO3): A kinetic and product study
Nathanael, Joses G.,Nuske, Madison R.,Richter, Annika,White, Jonathan M.,Wille, Uta
supporting information, p. 6949 - 6957 (2020/10/02)
Tertiary amides, such as in N-acylated proline or N-methyl glycine residues, react rapidly with nitrate radicals (NO3) with absolute rate coefficients in the range of 4-7 × 108 M-1 s-1 in acetonitrile. The major pathway proceeds through oxidative electron transfer (ET) at nitrogen, whereas hydrogen abstraction is only a minor contributor under these conditions. However, steric hindrance at the amide, for example by alkyl side chains at the α-carbon, lowers the rate coefficient by up to 75%, indicating that NO3-induced oxidation of amide bonds proceeds through initial formation of a charge transfer complex. Furthermore, the rate of oxidative damage of proline and N-methyl glycine is significantly influenced by its position in a peptide. Thus, neighbouring peptide bonds, particularly in the N-direction, reduce the electron density at the tertiary amide, which slows down the rate of ET by up to one order of magnitude. The results from these model studies suggest that the susceptibility of proline residues in peptides to radical-induced oxidative damage should be considerably reduced, compared with the single amino acid.
Synthesis and fluorescence properties of aminocyanopyrrole and aminocyanothiophene esthers for biomedical and bioimaging applications
Agrebi, Asma,Allouche, Fatma,Alves, Sérgio,Baleiz?o, Carlos,Cherif, Oussama,Farinha, José Paulo
, (2020/03/11)
We prepared a series of substituted aminocyanopyrroles and another of aminocynaothiophenes. We describe an efficient new one-step synthetic strategy via the condensation of an alkyl sarcosinate and ethoxymethylenemalononitrile, through a Gewald-like reaction. The UV–visible absorption and steady-state and time resolved fluorescence properties of some representative compounds, as well as their acid-base behavior, is also presented. The compounds might be useful for medicinal applications and as bioimaging probes.
BENZODICYCLOALKANE DERIVATIVE, PREPARATION METHOD AND USE THEREOF
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Paragraph 0174; 0175, (2019/06/19)
It is provided herein a benzobicycloalkane derivative, and a preparation method and use thereof. In particular, it is provided herein a compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, a preparation method, and a use thereof in preparation of drugs for treating pain.
4,5-Disubstituted 1-Methylimidazoles via Cyclization of Defined α-Aminoketones: Synthesis of Fungerin and Analogues I
Przybyla, Daniel,Nubbemeyer, Udo
supporting information, p. 770 - 774 (2017/02/15)
A protocol for the chemoselective synthesis of the fungal metabolite fungerin has been developed. First the required N-methyl α-aminoketone was generated starting from sarcosine, propiolic acid, and prenyl bromide. Marckwald thioimidazole cyclization and subsequent sulfur removal delivered the target fungerin as well as an analogue, respectively, displaying defined substitution patterns.
Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers
Otto, Nicola,Opatz, Till
supporting information; experimental part, p. 1105 - 1111 (2012/09/07)
In the search for new ligands for the Ullmann diaryl ether synthesis, permitting the coupling of electron-rich aryl bromides at relatively low temperatures, 56 structurally diverse multidentate ligands were screened in a model system that uses copper iodide in acetonitrile with potassium phosphate as the base. The ligands differed largely in their performance, but no privileged structural class could be identified.
Study of intramolecular aminolysis in peptides containing N-alkylamino acids at position 2
Ryakhovsky, Vladimir V.,Ivanov, Andrey S.
supporting information; experimental part, p. 7070 - 7076 (2012/08/29)
Many peptides and proteins, containing Nα-alkylamino acids (including proline) at the second position, are prone to intramolecular aminolysis (IA) with elimination of N-terminal dipeptide sequence as 2,5-diketopiperazines (DKP). We synthesized a series of short peptides, containing N-alkylamino acids at position 2, and studied their stability in the presence of acetic acid and amines. The presence of side chains in the second and the third amino acid residues and alkylation at Nα of the third amino acid residue slowed down IA. Nα-Alkyl residue in the first amino acid residue impeded IA only in peptides, containing three or more residues. Side chains of the first amino acids did not affect significantly the cleavage rates. Acetic acid promoted IA more strongly than aqueous ammonia, while tertiary amines were less effective. Peptides with methionine-S-oxide residues were more labile than the unoxidized analogs, suggesting intramolecular assistance of the S-oxide group in aminolysis. Surprisingly, intermediate compounds of the formula Boc-Met-MeXaa-Sar-NHR underwent rapid cleavage (endopeptolysis) upon attempted acidolytic deprotection.
Design, synthesis, and preliminary activity evaluation of novel peptidomimetics as aminopeptidase N/CD13 inhibitors
Li, Xun,Wang, Junli,Zhang, Lei,Xu, Wenfang
experimental part, p. 494 - 504 (2011/11/04)
The synthesis of a series of novel N-α-galloylated isoglutamic acid I-amide peptidomimetics is described. Their enzymatic inhibition against aminopeptidase N (APN/CD13) and matrix metalloproteinase-2 (MMP-2) was tested. The preliminary activity assay revealed that most of the compounds displayed selective inhibition against APN as compared with MMP-2, with IC50 values in a micromolar range. Within this series, compound 4 (IC 50a=10.2a±a.9μM) demonstrated comparable APN inhibition as compared with the positive control bestatin (IC 50a=a13.1aa0.7aμM), which might be a promising lead for further molecular optimizations. A new series of bi-peptide analogues containing amino acid or organic acid residues as elongated hydrophobic substituents inserting into S1 or S1 pocket was designed. Most of the target compounds showed potent and selective activities against APN/CD13 as compared with MMP-2. Compound 4 was comparable to bestatin and could be used as a potential lead for further development of APNIs.
Proline-rich proteins - Deriving a basis for residue-based selectivity in polyphenolic binding
Croft,Foley
supporting information; experimental part, p. 1594 - 1600 (2008/10/09)
1H NMR titration experiments have been used to establish that minimal proline-based models show enhanced binding selectivity towards phenol in CDCl3, relative to other similarly protected amino acid residues. Cooperative binding effects appear to play a role, with sarcosine models affording binding constants to phenol intermediate to those obtained from proline models and other amino acid models. The mechanism for binding, based on DFT calculations and the application of Hunter's molecular recognition toolbox model, cannot be solely attributed to hydrogen bond strength, and appears to be mediated through C-H-π bonds and the rotational freedom of the amide substrate. The Royal Society of Chemistry 2008.
Relationship between the hydrophobicity of dipeptides and the Michaelis-Menten constant Km of their hydrolysis by carboxypeptidase-Y and carboxypeptidase-A
Kanosue, Yoshifumi,Kojima, Satoshi,Hiraga, Yoshikazu,Ohkata, Katsuo
, p. 1187 - 1193 (2007/10/03)
The enzymatic hydrolysis of dipeptides by carboxypeptidase-Y and carboxypeptidase-A was investigated. In the enzymatic hydrolysis of the dipeptides, a good linear relationship (r = 0.997 and 0.999) was found between the Michaelis-Menten constant (Km) and the hydrophobicity of the substrates evaluated from relative elution volume in reversed-phase HPLC. The correlation suggests that the hydrophobicity of the C-terminal amino acid is a major factor in governing the stability of the enzyme-substrate complex. The difference in the slope of the linear-regression lines seems to reflect the degree of relative hydrophobicity of the binding pockets in carboxypeptidase-Y and carboxypeptidase-A.
Influence of solvent viscosity on the rate of hydrolysis of dipeptides by carboxypeptidase Y
Kanosue, Yoshifumi,Kojima, Satoshi,Ohkata, Katsuo
, p. 448 - 457 (2007/10/03)
The influence of solvent viscosity on the rate of enzymatic hydrolysis of a series of dipeptides (Z-Phe-Gly, Z-Phe-Sar, Z-Phe-Ala, Z-Phe-NMeAla, Z-Phe-Aib and Z-Phe-Pro) by carboxypeptidase Y was investigated. The effect of solvent viscosity on the enzymatic hydrolysis revealed that whereas all Kcat values decreased with viscosity, those of the N-alkyl peptides decreased more than those of the N-H peptides. The kinetic behaviour implies the involvement of conformational changes of the enzyme in terms of the 'induced-fit' process. Copyright
