Synthesis of new betulinic acid-peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity

Anastasiya I. Govdi, Nadezda V. Sokolova, Irina V. Sorokina, Dmitry S. Baev, Tatyana G. Tolstikova, Victor I. Mamatyuk, Dmitry S. Fadeev, Sergey F. Vasilevsky, Valentine G. Nenajdenko

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The modification of betulinic acid derivatives bearing an ethynyl group at the C-3 position by different azidopeptides using Cu(i)-catalyzed alkyne-azide cycloaddition has been described. All obtained compounds were tested for their anti-inflammatory activity using a histamine-induced paw edema model. Betulinic acid-peptide conjugates containing histidine, alanine, tryptophan and isoleucine amino acid fragments were found to exhibit high anti-inflammatory activity, comparable to that of indomethacin. It has been shown by molecular docking that the obtained conjugates are incorporated into the binding site of the protein Keap1 Kelch-domain by their amino acid residues and form more non-covalent bonds, but have lower affinity than the initial triterpenoid core. It has been suggested that peptide moieties can modify the activity of the initial triterpenoid scaffold due to the change in the conformational and thermodynamic characteristics, which have influence on the binding of the compound to its molecular target. This journal is

Original languageEnglish
Pages (from-to)230-238
Number of pages9
JournalMedChemComm
Volume6
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

Fingerprint

Computer Simulation
Anti-Inflammatory Agents
Bearings (structural)
Amino Acids
Peptides
Alkynes
Azides
Cycloaddition
Isoleucine
Cycloaddition Reaction
Thermodynamics
Histidine
Scaffolds
Tryptophan
Indomethacin
Alanine
Histamine
Edema
Carrier Proteins
Binding Sites

ASJC Scopus subject areas

  • Biochemistry
  • Pharmaceutical Science

Cite this

Govdi, A. I., Sokolova, N. V., Sorokina, I. V., Baev, D. S., Tolstikova, T. G., Mamatyuk, V. I., ... Nenajdenko, V. G. (2015). Synthesis of new betulinic acid-peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity. MedChemComm, 6(1), 230-238. https://doi.org/10.1039/c4md00236a

Synthesis of new betulinic acid-peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity. / Govdi, Anastasiya I.; Sokolova, Nadezda V.; Sorokina, Irina V.; Baev, Dmitry S.; Tolstikova, Tatyana G.; Mamatyuk, Victor I.; Fadeev, Dmitry S.; Vasilevsky, Sergey F.; Nenajdenko, Valentine G.

In: MedChemComm, Vol. 6, No. 1, 01.01.2015, p. 230-238.

Research output: Contribution to journalArticle

Govdi, AI, Sokolova, NV, Sorokina, IV, Baev, DS, Tolstikova, TG, Mamatyuk, VI, Fadeev, DS, Vasilevsky, SF & Nenajdenko, VG 2015, 'Synthesis of new betulinic acid-peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity', MedChemComm, vol. 6, no. 1, pp. 230-238. https://doi.org/10.1039/c4md00236a
Govdi, Anastasiya I. ; Sokolova, Nadezda V. ; Sorokina, Irina V. ; Baev, Dmitry S. ; Tolstikova, Tatyana G. ; Mamatyuk, Victor I. ; Fadeev, Dmitry S. ; Vasilevsky, Sergey F. ; Nenajdenko, Valentine G. / Synthesis of new betulinic acid-peptide conjugates and in vivo and in silico studies of the influence of peptide moieties on the triterpenoid core activity. In: MedChemComm. 2015 ; Vol. 6, No. 1. pp. 230-238.
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