The interaction of enantiomeric ketoprofen (KP) with BSA and HSA was studied by isothermal titration calorimetry (ITC). Affinity constants and thermodynamic parameters for complexation in two main protein sites were determined. Affinity constants for both proteins are generally lower for S(+)- than for R(-)-KP. Large enthalpic contributions to Gibbs free energy are compensated by large negative entropic terms for S(+) in the BSA-subdomain IIIA and HSA-subdomain IIA. The lowest energy BSA complexes of both enantiomers were structurally characterized by combining molecular mechanics (MM) and molecular dynamics (MD) with circular dichroism (CD). Comparison of quantum mechanically calculated rotational strengths with the CD signals of the complexes supported the structures. These allowed to identify the main interactions of the KP enantiomers with surrounding amino acids at short distances, that limit significantly KP mobility in both sites. In the primary binding site S(+) is close to Tyr 409 in subdomain IIIA (Sudlow site II), and R(-) is close to Trp 212 and His 240 in subdomain IIA (Sudlow site I). The same sites are involved in the formation of 2:1 complexes. The equilibrium structures are characterized by marked geometrical distortion of KP.

S. Monti, S. Ottani, F. Manoli, I. Manet, F. Scagnolari, B. Zambelli, et al. (2009). Chiral recognition of 2-(3-benzoylphenyl)propionic acid (ketoprofen) by serum albumin: an investigation with microcalorimetry, circular dichroism and molecular modelling. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 11, 9104-9113 [10.1039/b906021a].

Chiral recognition of 2-(3-benzoylphenyl)propionic acid (ketoprofen) by serum albumin: an investigation with microcalorimetry, circular dichroism and molecular modelling

OTTANI, STEFANO;SCAGNOLARI, FRANCESCO;ZAMBELLI, BARBARA;
2009

Abstract

The interaction of enantiomeric ketoprofen (KP) with BSA and HSA was studied by isothermal titration calorimetry (ITC). Affinity constants and thermodynamic parameters for complexation in two main protein sites were determined. Affinity constants for both proteins are generally lower for S(+)- than for R(-)-KP. Large enthalpic contributions to Gibbs free energy are compensated by large negative entropic terms for S(+) in the BSA-subdomain IIIA and HSA-subdomain IIA. The lowest energy BSA complexes of both enantiomers were structurally characterized by combining molecular mechanics (MM) and molecular dynamics (MD) with circular dichroism (CD). Comparison of quantum mechanically calculated rotational strengths with the CD signals of the complexes supported the structures. These allowed to identify the main interactions of the KP enantiomers with surrounding amino acids at short distances, that limit significantly KP mobility in both sites. In the primary binding site S(+) is close to Tyr 409 in subdomain IIIA (Sudlow site II), and R(-) is close to Trp 212 and His 240 in subdomain IIA (Sudlow site I). The same sites are involved in the formation of 2:1 complexes. The equilibrium structures are characterized by marked geometrical distortion of KP.
2009
S. Monti, S. Ottani, F. Manoli, I. Manet, F. Scagnolari, B. Zambelli, et al. (2009). Chiral recognition of 2-(3-benzoylphenyl)propionic acid (ketoprofen) by serum albumin: an investigation with microcalorimetry, circular dichroism and molecular modelling. PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 11, 9104-9113 [10.1039/b906021a].
S. Monti; S. Ottani; F. Manoli; I. Manet; F. Scagnolari; B. Zambelli; G. Marconi
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/86936
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 41
social impact