Biochemistry (Moscow)

, Volume 83, Issue 10, pp 1222–1230 | Cite as

Hydrophobic Derivatives of Glycopeptide Antibiotics as Inhibitors of Protein Kinases

  • G. Cozza
  • M. Fortuna
  • F. Meggio
  • S. Sarno
  • M. H. G. Kubbutat
  • F. Totzke
  • C. Schaechtele
  • L. A. Pinna
  • E. N. OlsufyevaEmail author
  • M. N. Preobrazhenskaya


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.


polycyclic glycopeptide derivatives protein kinases antiviral activity 



serine/threonine protein kinase (PK)


serine/threonine PK


tyrosine PK receptor UFO


serine/threonine PK proto-oncogene B-Raf

CDK2/Cyclin A

cyclin-dependent serine/threonine PK 2


host cells for HIV

CK1 and CK2

serine/threonine casein kinases 1 and 2


serine/threonine CK2 catalytic subunit isoform


host cells for FIPV


Dengue virus (flavivirus)


effective compound concentration required to inhibit host cell proliferation by 50%


feline infectious peritonitis virus (coronavirus)


hepatitis C virus (flavivirus)


human immunodeficiency virus (coronavirus)


host cells for HIV


compound concentration required to inhibit enzyme ctivity by 50%


insulin-like growth factor 1 receptor (tyrosine PK receptor)


Japanese encephalitis virus (flavivirus)


single pass tyrosine PK receptor


serine/threonine polo-like PK 1


serine/threonine PK N1


severe acute respiratory syndrome-associated coronavirus


proto-oncogene tyrosine PK c-Src (c-sarcoma)


tickborne encephalitis virus (flavivirus)


vascular endothelial growth factor tyrosine PK receptor


host cells for SARS-CoV, DENV-2, YFV-17D, JEV, and TBEV


yellow fever virus (flavivirus)


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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • G. Cozza
    • 1
  • M. Fortuna
    • 2
  • F. Meggio
    • 2
  • S. Sarno
    • 3
  • M. H. G. Kubbutat
    • 4
  • F. Totzke
    • 4
  • C. Schaechtele
    • 4
  • L. A. Pinna
    • 5
  • E. N. Olsufyeva
    • 6
    Email author
  • M. N. Preobrazhenskaya
    • 6
  1. 1.Department of Molecular MedicineUniversity of PadovaPadovaItaly
  2. 2.Department of Biological ChemistryUniversity of PadovaPadovaItaly
  3. 3.Department of Biomedical SciencesUniversity of PadovaPadovaItaly
  4. 4.ProQinase GmbHFreiburgGermany
  5. 5.Center for Neuroscience Research Neuroscience InstitutePadovaItaly
  6. 6.Gause Institute of New AntibioticsMoscowRussia

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