title: Interpretation of the dissolution of insoluble peptide sequences based on the acid-base properties of the solvent.
abstract: The dissolution process of model insoluble peptide sequences was investigated in view of the electron acceptor (AN) and electron donor (DN) solvent properties. The Alzheimer's disease-inducing (1-42) Abeta-amyloid peptide and its (1-21) fragment, the (66-97) transmembrane bradykinin B2 receptor sequence, and the strongly aggregated VVLGAAIV were selected as models of insoluble peptides. Solvents presenting similar AN and DN values failed, despite their polarities, to dissociate peptide chains (free in solution or bound to a polymer). The maximum solubility of these aggregated sequences was attained in solvents presenting the highest possible (AN-DN) values (in positive or negative mode). The AN-DN values ranged from approximately -20 to +80 and, notably, the lowest dissociation power was ascribed to solvents presenting values of approximately +40. The strong hydrogen bond donor water is located in this region, indicating that, for dissociation of specific insoluble segments, the solvent should appropriately combine its acid/base strength with the potential for van der Waals interactions. We also observed a sequence-dependent pH effect on peptide solubility confirmed through circular dichroism spectroscopy. This approach also revealed a complex but, in many cases, consistent influence of peptide conformation on its solubility degree, even when structure-inducing solvents were added. In conclusion, the random method of selecting solvents to dissolve insoluble and intractable peptide sequences, still in use by some, could be partially supplanted by the strategy described herein, which may be also applicable to other solute dissociation processes.
authors.affiliation: Department of Biophysics, Universidade Federal de São Paulo, CEP 04044-020, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Malavolta
authors.forename: Marcelo R S
authors.initials: MR
authors.lastname: Pinto
authors.forename: Jamile H
authors.initials: JH
authors.lastname: Cuvero
authors.forename: Clóvis R
authors.initials: CR
authors.lastname: Nakaie
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry; D002942:Circular Dichroism; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D043782:Receptor, Bradykinin B2 / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; D043782:Receptor, Bradykinin B2; D012997:Solvents; C075222:amyloid beta-protein (1-42); D014867:Water