Get access

Arginine–aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

Authors

  • Dhawal Shah,

    Corresponding author
    1. Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    Current affiliation:
    1. Middle East Technical University, Northern Cyprus Campus, Güzelyurt, KKTC, via Mersin 10, Turkey
    • Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    Search for more papers by this author
  • Jianguo Li,

    1. Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    Current affiliation:
    1. Singapore Eye Research Institute, Singapore.
    Search for more papers by this author
  • Abdul Rajjak Shaikh,

    1. Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    Current affiliation:
    1. KAUST Catalysis Center, King Abdullah University of Science and Technology, Kingdom of Saudi Arabia.
    Search for more papers by this author
  • Raj Rajagopalan

    Corresponding author
    1. Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    2. Dept. of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117576
    • Chemical & Pharmaceutical Engineering Program, The Singapore-MIT Alliance, National University of Singapore, Singapore 117576
    Search for more papers by this author

Abstract

We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, ΓXP, contrary to conventional thinking that positive ΓXP's indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine's preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine's interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on ΓXP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2012

Ancillary