1. A Novel Dipeptide Ligand of TSPO
O A Deeva, A S Pantileev, I V Rybina, M A Yarkova, T A Gudasheva, S B Seredenin Dokl Biochem Biophys. 2019 May;484(1):17-20. doi: 10.1134/S1607672919010046. Epub 2019 Apr 22.
On the basis of the first dipeptide ligand of TSPO, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), which was obtained by us earlier, we synthesized a new dipeptide, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102). GD-102 exhibited anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD-102 was one order of magnitude lower than that of GD-23. Compound PK11195, a selective antagonist of TSPO, completely blocked the anxiolytic activity of GD-102, which testified to the involvement of TSPO in the realization of the anxiolytic effect of GD-102. The results were confirmed by molecular docking data.
2. A novel C2 symmetric chiral stationary phase with N-[(4-Methylphenyl)sulfonyl]-l-leucine as chiral side chains
Junchen Zhu, Lunan Zhu, Yaling Wu, Lingping Cheng, Huiying Wang, Xiaotong Sun, Jiawei Shen, Yang Zhou, Yanxiong Ke J Sep Sci. 2020 Jun;43(12):2338-2348. doi: 10.1002/jssc.202000163. Epub 2020 May 28.
In this study, a series of chiral stationary phases based on N-[(4-methylphenyl)sulfonyl]-l-leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N-[(4-methylphenyl)sulfonyl]-l-leucine showed much better enantioselectivities than that based on N-(4-methylbenzoyl)-l-leucine amide. The construction of C2 symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C2 symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C2 symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π-π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans-N,N'-(1,2-diphenyl-1,2-ethanediyl)bis-acetamide, which had an excellent separation factor on the C2 symmetric chiral stationary phase, was investigated by 1 H-NMR spectroscopy and 2D 1 H-1 H nuclear overhauser enhancement spectroscopy.
3. Purification and enzymatic properties of an L-leucine aminopeptidase from swine liver
N Ledeme, G Hennon, O Vincent-Fiquet, R Plaquet Biochim Biophys Acta. 1981 Aug 13;660(2):262-70. doi: 10.1016/0005-2744(81)90169-8.
An L-leucine aminopeptidase (alpha-aminoacyl-peptide hydrolase (cytosol), EC 3.4.11.1), having a specificity toward the substrate L-leucine amide, but not toward L-leucyl beta-naphthylamide or L-leucyl p-nitroanilide, has been purified 332-fold from swine liver, with a yield of 8.6%. This is the first purification of this enzyme from hepatic tissue. The purified enzyme submitted to analytical electrophoresis on cellulose acetate strips or in polyacrylamide gel showed a single band after straining with Ponceau S Red dye or Amido black, respectively. Purified swine liver L-leucine aminopeptidase, a cytosol enzyme, exhibited a molecular weight of 268 000 +/- 50 000 by gel filtration. It hydrolyzed L-leucine amide substrate and L-leucyl peptides. It was activated by Mg2+ and Mn2+ and inhibited by Co2+ and Zn2+. The optimum pH was 10. It was rather sensitive to heat elevation. Swine liver L-leucine aminopeptidase was inhibited by EDTA, citric acid, isocaproic acid, dodecylamine, aliphatic alcohols and p-chloromercuribenzoate but unaffected by monoiodoacetic acid and diisopropyl fluorophosphate.
