Hydrophobic Derivatives of Glycopeptide Antibiotics as Inhibitors of Protein Kinases
- Authors: Cozza G.1, Fortuna M.2, Meggio F.2, Sarno S.3, Kubbutat M.H.4, Totzke F.4, Schaechtele C.4, Pinna L.A.5, Olsufyeva E.N.6, Preobrazhenskaya M.N.6
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Affiliations:
- 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
- Issue: Vol 83, No 10 (2018)
- Pages: 1222-1230
- Section: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151739
- DOI: https://doi.org/10.1134/S0006297918100073
- ID: 151739
Cite item
Abstract
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.
About the authors
G. Cozza
Department of Molecular Medicine
Email: eolsufeva@list.ru
Italy, Padova, 35131
M. Fortuna
Department of Biological Chemistry
Email: eolsufeva@list.ru
Italy, Padova, 35131
F. Meggio
Department of Biological Chemistry
Email: eolsufeva@list.ru
Italy, Padova, 35131
S. Sarno
Department of Biomedical Sciences
Email: eolsufeva@list.ru
Italy, Padova, 35131
M. H. G. Kubbutat
ProQinase GmbH
Email: eolsufeva@list.ru
Germany, Freiburg, 79106
F. Totzke
ProQinase GmbH
Email: eolsufeva@list.ru
Germany, Freiburg, 79106
C. Schaechtele
ProQinase GmbH
Email: eolsufeva@list.ru
Germany, Freiburg, 79106
L. A. Pinna
Center for Neuroscience Research Neuroscience Institute
Email: eolsufeva@list.ru
Italy, Padova, 35131
E. N. Olsufyeva
Gause Institute of New Antibiotics
Author for correspondence.
Email: eolsufeva@list.ru
Russian Federation, Moscow, 119021
M. N. Preobrazhenskaya
Gause Institute of New Antibiotics
Email: eolsufeva@list.ru
Russian Federation, Moscow, 119021
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