Role of chemical structure in molecular recognition by transferrin

Abstract

Studies of molecular recognition of chiral compounds by proteins are of importance from many points of view. The biological role of proteins in their interaction with small molecules is of fundamental interest and can be used in many different fields, for instance for in vitro analysis of optically active compounds. Studies in these areas need a detailed study of the interaction sites on the protein surface and the relationship between chemical structure and the complex formation ability of small molecules, such as drugs. The electrophoretic migration of charged compounds through a protein zone may provide information about the surface properties of the macromolecule in the interaction site. The interaction of human serum transferrin with tryptophan-methyl- (TME), ethyl- (TEE) and butyl-esters (TBE) has been investigated by capillary electrophoresis (CE) and model calculations. Differences in the separation of tryptophan derivatives were obtained by varying experimental parameters such as, pH, ionic strength of background electrolyte and the length of transferrin zone. Limited separation of the enantiomer pairs were observed at pH 5 and 7 with a maximum resolution at pH 6. The size of the ligands coupled to the chiral centre has importance in stereoselective recognition; however, a direct comparison of resolution different in same runs may lead to false conclusion if the experimental conditions are not comparable. With a careful evaluation of the data we obtained significant differences between the resolution of the smallest enantiomer pair compared to those of tryptophan derivatives with longer alkyl chains.

Role of chemical structure in stereoselective recognition of beta‐blockers and H1‐antihistamines by human serum transferrin in capillary zone electrophoresis

“…1). Comparing the three compounds the following notes should be made: (i) a strong interaction with transferrin is observed in the case of the three compounds (significant increase of the migration time is observed when transferrin is present in the capillary compared to the free zone electrophoresis experiments without transferrin); (ii) seemingly the resolution of mepindolol is not complete compared to bopindolol, but one must notify that the interaction time (due to the slower migration of bopindolol) is longer, which gives the opportunity to reach baseline resolution, compared to the faster movement of mepindolol (in which case no baseline resolution was obtained under the same conditions); similar results were obtained already with model compounds previously [13,18]; (iii) the benzoyl group in bopindolol should be responsible for the stronger interaction of bopindolol compared to pindolol and mepindolol. According to these findings chiral recognition can be significantly enhanced by hydrophobic interactions between the separand and separator.…”

“…b) 10 kV instead of 12 kV c) 15 kV instead of 12 kV different compounds [18]. This can be explained either by the conformational changes at pHs other than the pI of transferrin, or simply with the fact that transferrin is a serum protein and its function is optimal at neutral or nearly neutral condition.…”

Capillary electrophoresis of proteins 2005–2007

“…Complex formation between Cu(II) and BSA [177], Ca 21 and Mg 21 and human serum amyloid P component [178], tryptophan alkyl-esters and human serum transferrin [179], coumarin enantiomers and a 1 -glycoprotein genetic variants [180], arsenite and galectine-1 [181] have been investigated, too.…”

Cloning and overexpression of transferrin gene from cypermethrin-resistant Culex pipiens pallens

“…Of the ligands in the N-lobe, the histidine ligand shows the most variability in sequence. Furthermore, of note, four of the 12 insect transferrins have glutamic acid substituted for aspartic acid in the N-lobe (as seen in the bacterial ferric binding proteins) (Takatsy et al 2006;Gomme et al 2005). In addition, there is a widespread substitution of lysine for the anion binding arginine in the N-lobe in many organisms, including all of the fish, the sea squirt, and many of the unusual family members.…”