Structural Characterization of Monomers and Oligomers of D-Amino Acid-Containing Peptides Using T-Wave Ion Mobility Mass Spectrometry.
The D-residues are crucial to biological function of D-amino acid containing peptides (DAACPs). Previous ion mobility mass spectrometry (IM-MS) studies revealing oligomerization patterns of amyloid cascade demonstrated conversion from native soluble unstructured assembly to fibril ß-sheet oligomers, which has been implicated in amyloid diseases, such as Alzheimer's disease and type 2 diabetes. Although neuropeptides are typically present at very low concentrations in circulation, their local concentrations could be much higher in large dense core vesicles, forming dimers or oligomers. We studied the oligomerization of protonated and metal-adducted achatin I and dermorphin peptide isomers with IM-MS. Our results suggested that dimerization, oligomerization, and metal adduction augment the structural differences between D/L peptide isomers compared to protonated monomers. Dimers and oligomers enhanced the structural differences between D/L peptide isomers in both aqueous and organic solvent system. Furthermore, some oligomer forms were only observed for either D- or L-isomers, indicating the importance of chiral center in oligomerization process. The oligomerization patterns of D/L isomers appear to be similar. Potassium adducts were detected to enlarge the structural differences between D/L isomers. Graphical Abstract ᅟ.
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Xueqin
X
Pang
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA.|National Center for Protein Sciences-Beijing, Beijing Proteome Research Center, State Key Laboratory of Proteomics, Beijing Institute of Radiation Medicine, Beijing, 102206, China.
Chenxi
C
Jia
Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Zhengwei
Z
Chen
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA. lingjun.li@wisc.edu.|Department of Chemistry, University of Wisconsin-Madison, Madison, WI, 53705, USA. lingjun.li@wisc.edu.|School of Life Sciences, Tianjin University, Tianjin, China. lingjun.li@wisc.edu.
Lingjun
L
Li
D000596:Amino Acids / Q000737:chemistry; D000075663:Ion Mobility Spectrometry / Q000379:methods*; D007536:Isomerism; D000432:Methanol / Q000737:chemistry; D009479:Neuropeptides / Q000737:chemistry*; D018847:Opioid Peptides / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D000072757:Protein Conformation, beta-Strand; D055503:Protein Multimerization; D011522:Protons; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000596:Amino Acids; D009479:Neuropeptides; D018847:Opioid Peptides; D011522:Protons; D012997:Solvents; D014867:Water; C059927:achatin I; C030058:dermorphin; D011188:Potassium; D000432:Methanol
CCS; Collision cross-section; Conformational differences; D-amino acid containing peptides; DAACPs; Dimer; IM-MS; Ion mobility mass spectrometry; Metal adducts; Monomer; Native state; Oligomer; Oligomerization pattern; Organic solvent