Estimation of amyloid beta peptide chain global conformations at the Flory theta condition for different pH perturbations around the physiological solution value

JULIO A. DEIBER; MARTA B. PEIROTTI; MARÍA V. PIAGGIO

Santa Fe

Simposio; XI Simposio Argentino de Polímeros - SAP 2015; 2015

In previous works,electrokinetic and hydrodynamic properties of amyloid-beta (A?À) peptide chains(mainly A?À(1-42) with amino acid sequence (AAS) DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA) were estimated through the modeling of their effective electrophoreticmobilities. These property values were crucial to evaluate the propensities toaggregation of these complex polyampholitic chains arriving at usefulinformation concerning biophysical mechanisms associated, for instance, with theAlzheimer?Ls Disease. Nevertheless, data of the electrophoretic mobility ofamyloid beta peptides required at different values of pH, ionic strength I andtemperature T are quite scarce in the literature due to well known practicalreasons. This situation directs one to study polyampholite chain conformationsunder some idealized conditions through the knowledge of the AAS and aqueous solventproperties only. Therefore here we pursue this possibility by proposing the estimationof some A?À(1-42) peptide chain conformations at the chain-solvent Flory thetacondition for pH perturbations around the normal expected value (pH 7.4) of aphysiological solution, where the ionic strength I is around 150 mM (for cerebral spinalfluid the pH is slightly lower at around 7.3). In the present work the chargeregulation effect is neglected, as a first approximation, by assuming that thesechains are sensing the pH of the bulk solution. Although this effect isrelevant to quantify the pH shift toward the chain pI to get the near moleculepH, relevant information concerning A?À peptide conformations at different pHvalues is still promising as described in this work. For instance, within thisframework the conformational state of the A?À(1-42) chain at pH 7.4 and I=150 mMis in the transition from hybrid to collapsed globule regimens. This type ofresult may be a useful guide for subsequent numerical calculations of A?À peptideconformations when the experimental data required are available