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

Hélia F. Jeremias, Diana Lousa, Axel Hollmann, Ana C. Coelho, Carla S. Baltazar, João D. Seixas, Ana R. Marques, Nuno C. Santos, Carlos C. Romão, Cláudio M. Soares

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Abstract

Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions 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 future CORM design.

Original languageEnglish
Article numbere0204624
JournalPLoS ONE
Volume13
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

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Molybdenum
molybdenum
Carbon Monoxide
bovine serum albumin
Bovine Serum Albumin
carbon monoxide
Molecules
prototypes
Prodrugs
methodology
hydrogen bonding
molecular dynamics
transport proteins
blood proteins
clinical trials
Coordination Complexes
Molecular Dynamics Simulation
Hydrogen Bonding
Computational methods
metals

Cite this

@article{e712f1d0e7b74d4fbb049c2d401f2616,
title = "Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods",
abstract = "Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions 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 future CORM design.",
author = "Jeremias, {H{\'e}lia F.} and Diana Lousa and Axel Hollmann and Coelho, {Ana C.} and Baltazar, {Carla S.} and Seixas, {Jo{\~a}o D.} and Marques, {Ana R.} and Santos, {Nuno C.} and Rom{\~a}o, {Carlos C.} and Soares, {Cl{\'a}udio M.}",
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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.

In: PLoS ONE, Vol. 13, No. 9, e0204624, 01.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods

AU - Jeremias, Hélia F.

AU - Lousa, Diana

AU - Hollmann, Axel

AU - Coelho, Ana C.

AU - Baltazar, Carla S.

AU - Seixas, João D.

AU - Marques, Ana R.

AU - Santos, Nuno C.

AU - Romão, Carlos C.

AU - Soares, Cláudio M.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions 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 future CORM design.

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JF - PlosOne

SN - 1932-6203

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