JOURNAL ARTICLE

Molecular insight into the ligand-IgG interactions for 4-mercaptoethyl-pyridine based hydrophobic charge-induction chromatography

Dong-Qiang Lin, Hong-Fei Tong, Hong-Yin Wang, Shan-Jing Yao
Journal of Physical Chemistry. B 2012 February 2, 116 (4): 1393-400
22214397
Hydrophobic charge-induction chromatography (HCIC) with 4-mercaptoethyl-pyridine (MEP) as the ligand is a novel technology for antibody purification. In the present work, the molecular simulation methods were used to investigate the interactions between MEP ligand and Fc fragment of IgG (Fc-A). Six ligands with different structures of spacer arm were studied with molecular docking and dynamics simulation at neutral and acidic pH. The binding modes and the interaction energies were analyzed. The results indicated that all ligands tested could bind into the selected pocket on the C(H2) domain of Fc-A at neutral pH. The pyridine ring on the top of MEP ligands acts as a major role to provide the hydrophobic association and hydrogen bond for the ligand-IgG binding; meanwhile, the sulfone group on the spacer arm might form the additional hydrogen bond and enhance the binding of ligand onto the surface of IgG. The replacements of thioether sulfur atom on the spacer arm with either nitrogen or oxygen atom seem to have little influence on the binding. The influences of pH on the ligand-IgG interactions were also studied with the molecular dynamics simulation. It was found that MEP ligands would departed from the surface of Fc-A at low pH due to the electrostatic repulsion. The ligands with a sulfone group on the spacer arm would weaken the electrostatic repulsion and need more acidic conditions for the departing of ligand. The molecular simulation results were in agreement with some experimental observations, which would be useful to elucidate the molecular mechanism of HCIC and design a novel ligand to improve the efficiency of antibody separation.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
22214397
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"