Processing of serum proteins underlies the mass spectral fingerprinting of myocardial infarction.
The MALDI-TOF spectra of peptides from the sera of normal and myocardial infarction patients produced patterns that provided an accurate diagnostic of MI. In myocardial infarction, the spectral pattern originated from the cleavage of complement C3 alpha chain to release the C3f peptide and cleavage of fibrinogen to release peptide A. The fibrinogen peptide A and complement C3f peptide were in turn progressively truncated by aminopeptidases to produce two families of fragments that formed the characteristic spectral pattern of MI. Time course and inhibitor studies demonstrated that the peptide patterns in the serum reflect the balance of disease-specific-protease and aminopeptidase activity ex vivo.
Marshall
John
J
SYNX PHARMA, 1 Marmac Drive, Toronto, Ontario, Canada M9W 1E7. jmarshall@synxpharma.com
Kupchak
Peter
P
Zhu
Weimin
W
Yantha
Jason
J
Vrees
Tammy
T
Furesz
Shirley
S
Jacks
Kellie
K
Smith
Chris
C
Kireeva
Inga
I
Zhang
Rulin
R
Takahashi
Miyoko
M
Stanton
Eric
E
Jackowski
George
G
D000595:Amino Acid Sequence; D000704:Analysis of Variance; D001798:Blood Proteins / Q000032:analysis*; D015153:Blotting, Western; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D001330:Electronic Data Processing / Q000379:methods; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D010449:Peptide Mapping / Q000379:methods*; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors
D001798:Blood Proteins; D003176:Complement C3; D011480:Protease Inhibitors; C046821:complement C3f; C464794:fibrinogen Aalpha; D010664:Phenylmethylsulfonyl Fluoride; D003179:Complement C3b; D005340:Fibrinogen; D010447:Peptide Hydrolases