Hydrophobic Derivatives of Glycopeptide Antibiotics as Inhibitors of Protein Kinases
- 作者: Cozza G.1, Fortuna M.2, Meggio F.2, Sarno S.3, Kubbutat M.4, Totzke F.4, Schaechtele C.4, Pinna L.5, Olsufyeva E.6, Preobrazhenskaya M.6
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隶属关系:
- Department of Molecular Medicine
- Department of Biological Chemistry
- Department of Biomedical Sciences
- ProQinase GmbH
- Center for Neuroscience Research Neuroscience Institute
- Gause Institute of New Antibiotics
- 期: 卷 83, 编号 10 (2018)
- 页面: 1222-1230
- 栏目: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151739
- DOI: https://doi.org/10.1134/S0006297918100073
- ID: 151739
如何引用文章
详细
As key regulators of cell signaling, protein kinases (PKs) are attractive targets for therapeutic intervention in a variety of diseases. Herein, we report for the first time the inhibitory activity of polycyclic peptides, particularly, derivatives of glycopeptide antibiotics teicoplanin and eremomycin, against a panel of 12 recombinant human protein kinases and two protein kinases (CK1 and CK2) isolated from rat liver. Several of the investigated compounds inhibited various PKs with IC50 values below 10 μM and caused >90% suppression of the enzyme activity at 10 μM concentration. Kinetic analysis of the protein kinase CK2α inhibition by the teicoplanin aglycon analogue (7) demonstrated the non-competitive mechanism of inhibition (with regard to ATP). Interestingly, the inhibitory activity of some investigated compounds correlated with the earlier described antiviral activity against HIV, HCV, and other corona- and flaviviruses.
作者简介
G. Cozza
Department of Molecular Medicine
Email: eolsufeva@list.ru
意大利, Padova, 35131
M. Fortuna
Department of Biological Chemistry
Email: eolsufeva@list.ru
意大利, Padova, 35131
F. Meggio
Department of Biological Chemistry
Email: eolsufeva@list.ru
意大利, Padova, 35131
S. Sarno
Department of Biomedical Sciences
Email: eolsufeva@list.ru
意大利, Padova, 35131
M. Kubbutat
ProQinase GmbH
Email: eolsufeva@list.ru
德国, Freiburg, 79106
F. Totzke
ProQinase GmbH
Email: eolsufeva@list.ru
德国, Freiburg, 79106
C. Schaechtele
ProQinase GmbH
Email: eolsufeva@list.ru
德国, Freiburg, 79106
L. Pinna
Center for Neuroscience Research Neuroscience Institute
Email: eolsufeva@list.ru
意大利, Padova, 35131
E. Olsufyeva
Gause Institute of New Antibiotics
编辑信件的主要联系方式.
Email: eolsufeva@list.ru
俄罗斯联邦, Moscow, 119021
M. Preobrazhenskaya
Gause Institute of New Antibiotics
Email: eolsufeva@list.ru
俄罗斯联邦, Moscow, 119021