TY - JOUR
T1 - Effect of secondary interactions, steric hindrance and electric charge on the interaction of VIVO species with proteins
AU - Sciortino, Giuseppe
AU - Sanna, Daniele
AU - Ugone, Valeria
AU - Maréchal, Jean Didier
AU - Alemany-Chavarria, Mercè
AU - Garribba, Eugenio
N1 - Publisher Copyright:
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
PY - 2019
Y1 - 2019
N2 - The interaction of two bis-chelated VIVO2+ species, formed by pipemidic (Hpip) and 8-hydroxyquinoline-5-sulphonic acids (H2hqs), with two small proteins, ubiquitin (Ub) and lysozyme (Lyz), was studied by EPR, ESI-MS, docking and DFT methods. The two complexes differ in electric charge (at neutral pH it is +2 and-2 for the species of Hpip and H2hqs, respectively), coordination geometry (cis-[VO(Hpip)2(H2O)]2+ is in equilibrium with the square pyramidal [VO(Hpip)2]2+, while cis-[VO(hqs)2(H2O)]2- is the only species in solution), and size (pipemidic acid is more sterically crowded than 8-hydroxyquinoline-5-sulphonic acid). The ESI-MS spectra showed that the number of cis-VO(hqs)22- moieties which interact with Ub is twice that of cis-VO(Hpip)22+ (adducts with formula n[VOL2]-Ub, where n = 1-4 for H2hqs and n = 1-2 for Hpip, were detected). The data can be rationalized in terms of the lower steric requirements of hqs2- and its negative charge, which favour secondary interactions with the surface groups of the protein. The EPR spectra revealed the coordination of Asp/Glu-COO or His-N donors, while docking calculations allowed us to identify the Ub residues involved in the VO(Hpip)2 (Asp39 and His68) and VO(hqs)2 binding (Glu18, Asp39, Asp58 and His68). The steric hindrance of Hpip is so important that the interaction of cis-[VO(Hpip)2(H2O)]2+ with lysozyme is completely prevented, while with cis-[VO(hqs)2(H2O)]2- the adducts n[VO(hqs)2]-Lyz (n = 1-2) were detected. Finally, the general effect of secondary interactions such as hydrogen bonds and van der Waals contacts, steric hindrance and electric charge on the V binding and stability of the adducts formed is also discussed, suggesting that these factors should be taken into account when designing new pharmacologically active compounds.
AB - The interaction of two bis-chelated VIVO2+ species, formed by pipemidic (Hpip) and 8-hydroxyquinoline-5-sulphonic acids (H2hqs), with two small proteins, ubiquitin (Ub) and lysozyme (Lyz), was studied by EPR, ESI-MS, docking and DFT methods. The two complexes differ in electric charge (at neutral pH it is +2 and-2 for the species of Hpip and H2hqs, respectively), coordination geometry (cis-[VO(Hpip)2(H2O)]2+ is in equilibrium with the square pyramidal [VO(Hpip)2]2+, while cis-[VO(hqs)2(H2O)]2- is the only species in solution), and size (pipemidic acid is more sterically crowded than 8-hydroxyquinoline-5-sulphonic acid). The ESI-MS spectra showed that the number of cis-VO(hqs)22- moieties which interact with Ub is twice that of cis-VO(Hpip)22+ (adducts with formula n[VOL2]-Ub, where n = 1-4 for H2hqs and n = 1-2 for Hpip, were detected). The data can be rationalized in terms of the lower steric requirements of hqs2- and its negative charge, which favour secondary interactions with the surface groups of the protein. The EPR spectra revealed the coordination of Asp/Glu-COO or His-N donors, while docking calculations allowed us to identify the Ub residues involved in the VO(Hpip)2 (Asp39 and His68) and VO(hqs)2 binding (Glu18, Asp39, Asp58 and His68). The steric hindrance of Hpip is so important that the interaction of cis-[VO(Hpip)2(H2O)]2+ with lysozyme is completely prevented, while with cis-[VO(hqs)2(H2O)]2- the adducts n[VO(hqs)2]-Lyz (n = 1-2) were detected. Finally, the general effect of secondary interactions such as hydrogen bonds and van der Waals contacts, steric hindrance and electric charge on the V binding and stability of the adducts formed is also discussed, suggesting that these factors should be taken into account when designing new pharmacologically active compounds.
UR - http://www.scopus.com/inward/record.url?scp=85069968772&partnerID=8YFLogxK
U2 - 10.1039/c9nj01956a
DO - 10.1039/c9nj01956a
M3 - Article
AN - SCOPUS:85069968772
SN - 1144-0546
VL - 43
SP - 17647
EP - 17660
JO - New Journal of Chemistry
JF - New Journal of Chemistry
IS - 45
ER -