Multiple and Variable Binding of Pharmacologically Active Bis(maltolato)oxidovanadium(IV) to Lysozyme
Ferraro, Giarita (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)
Paolillo, Maddalena (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)
Sciortino, Giuseppe (Institut d'Investigacions Químiques de Catalunya)
Garribba, Eugenio (Università di Sassari. Dipartimento di Medicina, Chirurgia e Farmacia)
Merlino, Antonello (Università degli Studi di Napoli Federico II. Dipartimento di Scienze Chimiche)

Data:	2022
Resum:	The interaction with proteins of metal-based drugs plays a crucial role in their transport, mechanism, and activity. For an active MLn complex, where L is the organic carrier, various binding modes (covalent and non-covalent, single or multiple) may occur and several metal moieties (M, ML, ML2, etc. ) may interact with proteins. In this study, we have evaluated the interaction of [VIVO(malt)2] (bis(maltolato)oxidovanadium(IV) or BMOV, where malt = maltolato, i. e. , the common name for 3-hydroxy-2-methyl-4H-pyran-4-onato) with the model protein hen egg white lysozyme (HEWL) by electrospray ionization mass spectrometry, electron paramagnetic resonance, and X-ray crystallography. The multiple binding of different V-containing isomers and enantiomers to different sites of HEWL is observed. The data indicate both non-covalent binding of cis-[VO(malt)2(H2O)] and [VO(malt)(H2O)3]+ and covalent binding of [VO(H2O)3-4]2+ and cis-[VO(malt)2] and other V-containing fragments to the side chains of Glu35, Asp48, Asn65, Asp87, and Asp119 and to the C-terminal carboxylate. Our results suggest that the multiple and variable interactions of potential VIVOL2 drugs with proteins can help to better understand their solution chemistry and contribute to define the molecular basis of the mechanism of action of these intriguing molecules.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Inorganic chemistry, Vol. 61, Issue 41 (October 2022) , p. 16458-16467, ISSN 1520-510X

DOI: 10.1021/acs.inorgchem.2c02690
PMID: 36205235

10 p, 5.0 MB

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