Abstract

The monomer and oligomer peptide complexes of the amyloidogenic human islet amyloid polypeptide 1-19 (hIAPP19) and non-amyloidogenic rat islet amyloid polypeptide 1-19 (rIAPP19) were investigated using electrospray ionization (ESI)-mass spectrometry (MS). The dissociation of monomers and oligomers was investigated by tandem mass spectrometry (MS/MS) using collision-induced dissociation (CID). Peptide bond dissociation in the Arg8–Ser19 region of hIAPP19 was mainly observed in the tandem mass spectra of the monomers and oligomers. The fragmentation pattern of the hIAPP19 D 3+ (= [dimer+3H] 3+ ) complex was similar to that of the M 2+ (= [monomer+2H] 2+ ) tandem mass spectrum in the form of {M + (frag- ment ion of M 2+ )}. In the case of the hIAPP T 4+ (= [trimer+4H] 4+ ) complex, the (monomer–D 3+ ) 4+ complex geometry was assumed to be stable based on the presence of {M + (fragment ion of D 3+ )} ions in the tandem mass spectrum of the T 4+ complex. The interaction geometry of [(disulfide bond (S-S) in Cys2 - Cys7 region)–((S-S) in Cys2 - Cys7 region)] was proposed for the dimer and trimer complexes of hIAPP19 based on the observation of three characteristic fragment ions: (i) [M- S] 2+ , [M+S] 2+ , [D-S] 3+ , and [D+S] 3+ , (ii) y 18 , and (iii) b u (u = 8–18) fragment ion series in the Arg8 - Ser19 region. The tandem mass spectrum of rIAPP19 differed from that of hIAPP19. Fragment ions originating from the Cys2–Cys7 region were observed in the M 2+ tandem mass spectrum of rIAPP19 as [y n +S] 2+ (n = 13 – 17) and [z n +S] 2+ (n = 13 – 15).