Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions

Jianguo Li, Manju Garg, Dhawal Shah, Raj Rajagopalan

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Experiments hold intriguing, circumstantial clues to the mechanisms behind arginine-mediated solubilization of small organic drugs and suppression of protein aggregation driven by hydrophobic or aromatic associations, but how exactly arginine's molecular structure and interactions contribute to its function remains unclear since attention has focused so far on the thermodynamics of the preferential exclusion or binding of arginine. Here, we examine, through molecular dynamics simulations, how arginine solubilizes nanoscale particles with hydrophobic surfaces or aromatic-ring-type surface interactions. We show that preferential, hydrophobic, and dispersion interactions of arginine's guanidinium group with the particles lead to a surfactant-like behavior of arginine around the particles and to a solvation layer with a protective polar mask creating a hydrophilic shell. Additionally, arginine-arginine association around the solvation layer further prevents aggregative contacts. The results shed some light on the mechanistic basis of arginine's function as a suppressant of protein aggregation, although the complex energy landscapes and kinetic pathways of aggregation are protein-dependent and pose formidable challenges to developing comprehensive mechanistic pictures. Our results suggest arginine's mode of interaction with hydrophobic patches and aromatic residues could reduce aggregation-prone intermediate states of proteins and shield protein-protein aggregative contacts. The approach used here offers a systematic way of exploring implications of other amino acid/excipient interactions by studying interactions of the excipient with particles grafted with amino acids.

Original languageEnglish
Article number054902
JournalJournal of Chemical Physics
Volume133
Issue number5
DOIs
Publication statusPublished - Aug 7 2010

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Arginine
aqueous solutions
proteins
Agglomeration
solvation
amino acids
Proteins
interactions
Excipients
Solvation
Hydrophobic and Hydrophilic Interactions
molecular interactions
exclusion
surface reactions
drugs
molecular structure
masks
Amino Acids
surfactants
retarding

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry
  • Medicine(all)

Cite this

Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions. / Li, Jianguo; Garg, Manju; Shah, Dhawal; Rajagopalan, Raj.

In: Journal of Chemical Physics, Vol. 133, No. 5, 054902, 07.08.2010.

Research output: Contribution to journalArticle

Li, Jianguo ; Garg, Manju ; Shah, Dhawal ; Rajagopalan, Raj. / Solubilization of aromatic and hydrophobic moieties by arginine in aqueous solutions. In: Journal of Chemical Physics. 2010 ; Vol. 133, No. 5.
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