Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods

JEREMIAS, HÉLIA F.; LOUSA, DIANA; HOLLMANN, AXEL; COELHO, ANA C.; BALTAZAR, CARLA S.; SEIXAS, JOÃO D.; MARQUES, ANA R.; SANTOS, NUNO C.; ROMÃO, CARLOS C.; SOARES, CLÁUDIO M.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018 vol. 13

1932-6203

Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet thealternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous.These molecules are designed to release carbon monoxide in specific tissues, inresponse to some locally expressed stimulus, where CO can trigger a cytoprotectiveresponse. The design of such prodrugs, mostly metal carbonyl complexes, must considertheir ADMET profiles, including their interaction with transport plasma proteins. However,the molecular details of this interaction remain elusive. To shed light into this matter, wefocused on the CORM prototype [Mo(η5-Cp)(CH2COOH)(CO)3] (ALF414) and performed adetailed molecular characterization of its interaction with bovine serum albumin (BSA),using spectroscopic and computational methods. The experimental results show thatALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondarystructure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism,indicating that no stable complex is formed between the protein Trp residues andALF414. The molecular dynamics simulations are in good agreement with the experimentalresults and confirm the dynamic and unspecific character of the interaction betweenALF414 and BSA. The simulations also provide important insights into the nature of theinteractions of this CORM prototype with BSA, which are dominated by hydrophobic contacts,with a contribution from hydrogen bonding. This kind of information is useful for futureCORM design.