Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric imaging of synthetic polymer sample spots prepared using ionic liquid matrices

2014 ◽  
Vol 28 (5) ◽  
pp. 489-498 ◽  
Author(s):  
Stefan J. Gabriel ◽  
Dietmar Pfeifer ◽  
Clemens Schwarzinger ◽  
Ulrich Panne ◽  
Steffen M. Weidner
2000 ◽  
Vol 46 (9) ◽  
pp. 1293-1300 ◽  
Author(s):  
Jonas Bergquist ◽  
Oluf Andersen ◽  
Ann Westman

Abstract Background: Familial amyloidotic polyneuropathy (FAP) type I, the most common dominantly inherited form of amyloidosis, is caused by a Val-to-Met point mutation at position 30 (Val30→Met) in the protein transthyretin. Mass spectrometric analysis can identify modification of proteins, such as point mutations, acetylation, phosphorylation, sulfation, oxidation, and glycosylation. Methods: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) spectra from cerebrospinal fluid (CSF) drawn from a patient with FAP were compared with CSF from controls. We also isolated transthyretin with a Centrisart molecular size cutoff filter and performed high-accuracy peptide mass mapping to localize the site of the amino acid substitution (Val30→Met). Results: Mass spectra of transthyretin were produced directly from human CSF as well as from CSF after a simple prepurification method without immunoprecipitation. On-target tryptic digestion and MALDI-MS verified mass spectrometric peak identification. The point mutation was still detectable in CSF after hepatic transplantation. Conclusions: It is possible to diagnose FAP by a rapid MALDI-TOF MS analysis using only 100 μL of CSF, with only 250 nL actually consumed on target. The approach may also be useful to monitor production of mutated transthyretin by choroid plexus, especially after liver transplantation.


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