P.F.S.R.L. - AMYLIN
Introduction
One of the major pathologies associated with non-insulin-dependent
diabetes mellitus (NIDDM) is the formation of amyloid deposits, composed
of high molecular weight aggregates of the islet amyloid polypeptide
(IAPP). In our study we use an aggregable fragment of human IAPP (hIAPP)
(amino acids 20-29) to investigate the effects of electrostatic
interactions on the aggregation properties of the peptide, as well as the
effects of trifluoroethanol (TFE) on peptide aggregation and conformation.
We monitor the aggregation of the hIAPP fragment in solutions of pH
ranging from 4.6 to 9.4. The aggregation rate peaks at pH of ca 5-6,
indicating that the charged groups that are titrated at both high and low
pH facilitate the aggregation. The aggregation of the hIAPP fragments has
also been monitored in neutral buffer containing various concentrations of
NaCl. Charge shielding by increasing NaCl concentrations resulted in
prolonged lag time to aggregation. Fractional concentrations of TFE as low
as 1% (v/v) in solutions were found to inhibit aggregation of the peptide
completely. Circular dichroism (CD) studies of the hIAPP fragment in
various concentrations of TFE show that structural shifts in the fragment
occur very slowly, as long as seven days after addition of TFE to the
peptide solutions.
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