TY  - JOUR
A1  - Abbas, Ioana M.
A1  - Vranic, Marija
A1  - Hoffmann, Holger
A1  - El-Khatib, Ahmed H.
A1  - Montes-Bayón, María
A1  - Möller, Heiko Michael
A1  - Weller, Michael G.
T1  - Investigations of the Copper Peptide Hepcidin-25 by
LC-MS/MS and NMR⁺
JF  - International Journal of Molecular Sciences
N2  - Hepcidin-25 was identified as themain iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II) binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandemmass spectrometry (MS/MS), high-resolutionmass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D)model of hepcidin-25with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or referencematerial comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.
KW  - hepcidin-25
KW  - copper
KW  - nickel
KW  - copper complex
KW  - ATCUN motif
KW  - metal complex
KW  - MS
KW  - NMR structure
KW  - metal peptide
KW  - metalloprotein
KW  - metallopeptide
KW  - isomerization
KW  - racemization
KW  - purity
KW  - reference material
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19082271
SN  - 1422-0067
SN  - 1661-6596
VL  - 19
IS  - 8
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Starke, Ines
A1  - Koch, Andreas
A1  - Kammer, Stefan
A1  - Holdt, Hans-Jürgen
A1  - Möller, Heiko Michael
T1  - Electrospray mass spectrometry and molecular modeling study of formation and stability of silver complexes with diazaperylene and bisisoquinoline
JF  - Journal of mass spectrometry
N2  - The complex formation of the following diazaperylene ligands (L) 1,12-diazaperylene 1, 1,1-bisisoquinoline 2, 2,11-disubstituted 1,12-diazaperylenes (alkyl=methyl, ethyl, isopropyl, 3, 5, 7), 3,3-disubstituted 1,1-bisisoquinoline (alkyl=methyl, ethyl, isopropyl, 4, 6, 8 and with R=phenyl, 11 and with pyridine 12), and the 5,8-dimethoxy-substituted diazaperylene 9, 6,6-dimethoxy-substituted bisisoquinoline 10 with AgBF4 was investigated. Collision-induced dissociation measurements were used to evaluate the relative stabilities of the ligands themselves and for the [1:1](+) complexes as well as for the homoleptic and heteroleptic silver [1:2](+) complexes in the gas phase. This method is very useful in rapid screening of the stabilities of new complexes in the gas phase. The influence of the spatial arrangement of the ligands and the type of substituents employed for the complexation were examined. The effect of the preorganization of the diazaperylene on the threshold activation voltages and thus of the relative binding energies of the different complexes are discussed. Density functional theory calculations were used to calculate the optimized structures of the silver complexes and compared with the stabilities of the complexes in the gas phase for the first time.
KW  - electrospray ionization mass spectrometry and modeling
KW  - silver(1) complexes
KW  - stability
Y1  - 2018
U6  - https://doi.org/10.1002/jms.4071
SN  - 1076-5174
SN  - 1096-9888
VL  - 53
IS  - 5
SP  - 408
EP  - 418
PB  - Wiley
CY  - Hoboken
ER  -