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

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 Full article

Journal

MedChemComm
ISSN: 2040-2503 , E-ISSN: 2040-2511

Output data

Year: 2015, Volume: 6, Number: 1, Pages: 230-238 Pages count : DOI: 10.1039/c4md00236a

Authors

Govdi Anastasiya I. ¹ , Sokolova Nadezda V. ² , Sorokina Irina V. ³ , Baev Dmitry S. ³ , Tolstikova Tatyana G. ³ , Mamatyuk Victor I. ³ , Fadeev Dmitry S. ³ , Vasilevsky Sergey F. ^1,3 , Nenajdenko Valentine G. ^4,2

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Kinet & Combust, Novosibirsk 630090, Russia
2	(Данные Web of science) Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia
3	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk 630090, Russia
4	(Данные Web of science) Russian Acad Sci, AN Nesmeyanov Inst Organoelement Cpds, Moscow 119991, Russia

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.

Govdi A.I. , Sokolova N.V. , Sorokina I.V. , Baev D.S. , Tolstikova T.G. , Mamatyuk V.I. , Fadeev D.S. , Vasilevsky S.F. , Nenajdenko V.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
MedChemComm. 2015. V.6. N1. P.230-238. DOI: 10.1039/c4md00236a WOS Scopus РИНЦ

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