Total Chemical Synthesis of Islet Amyloid Polypeptide and its Precursors for Membrane Interaction Studies

摘要

The human islet amyloid polypeptide, also known as hIAPP or amylin, is a 37-residue peptide that is the major component of the amyloid deposits frequently found in patients suffering from diabetes mellitus type 2 [1]. Although it is not yet clear whether these amyloid deposits are a cause, consequence or side effect of the disease, it is hypothesized that the interaction between hIAPP and cellular membranes is a cause of IAPP cytotoxicity, leading to P-cell death [2]. To provide further insights in the interaction between cell membranes and IAPP, we chemically synthesized human (h) and murine (m) IAPP precursors (ProhlAPP, ProhIAPPt^8, PromIAPP and PromlAPP_(1-51) as well as mature IAPP (m/h) [3]. mIAPP differs at only 6 residues from hIAPP but is known not to aggregate into amyloid deposits. In addition, we also prepared fluorescently labeled derivatives of mature IAPP (m/h) (Figure 1).