ENHANCED SOLUBILITY OF PROTEINS AND PEPTIDES IN NONPOLAR-SOLVENTS THROUGH HYDROPHOBIC ION-PAIRING

A new technique for enhancing the solubility of peptides and proteins in organic solvents is described. Complexation of polypeptides with st oichiometric amounts of an anionic detergent, such as sodium dodecyl s ulfate (SDS), produces diminished aqueous solubility, but enhanced sol ubility in organic solvents. Consequently, the partitioning of a polyp eptide into a nonpolar solvent can be increased by two to four orders of magnitude. In the case of an insulin-SDS complex, the solubility in 1-octanol is more than tenfold greater than in water. In 1-octanol, t he native structure of insulin remains intact, as determined by CD spe ctroscopy, and the thermal denaturation temperature (T(m)) is increase d by approximately 50-degrees-C relative to unfolding in water. Finall y, peptides and proteins can be extracted back into an aqueous phase p rovided the chloride concentration is sufficient to displace bound det ergent molecules.