The anchoring ability of specific non-coordinating side chains in fragments of the rat and the human amylin

Amylin is a 37-residue peptide hormone cosecreted with insulin by pancreatic ?- cells. It is the principal constituent of the amyloid deposits that form in the islets of Lagerhans in patients with type-2 diabetes mellitus. However rat amylin does not form amyloid-like fibrils. The main difference is in the two sequences that histidine is not present in rat amylin. Despite the lack of any common strongly coordinating donor functions this peptide is able to bind metal ions. According to our earlier results the hexapeptide domain -VRSSNN- can be the main metal binding sequence. For getting more information about metal binding of rat and the human amylin, fragment and their mutants have been synthesized and their metal complexes studied by pH-potentiometric, UV-Vis, CD and ESR spectroscopic methods. The peptides were synthesized in N-terminally free forms, NH2-VRSSNN-NH2, NH2- VRSSAA-NH2, NH2-VRAANN-NH2, NH2-VRSS-NH2, NH2-SSNN-NH2 and NH2- AANN-NH2, NH2-GGHSSNN-NH2, providing a possibility for the comparison of the metal binding abilities of the amino terminus and the -SSNN- domain. During our studies we focused the next questions: What kind of changes can be seen in the metal binding ability of peptides with free terminus compared to the protected ones? What is the role of the -SSNN- sequence and the asparagine residues? In case of longer fragments (NH2-VRSSNN-NH2, NH2-GGHSSNN-NH2) we wondered if they were able to bind more than one equivalent metal ion? Are these peptides suitable for mimicking the metal binding site of the rat or human amylin?