Quantitative Structure Activity Relationship Studies of 4-Methyl-2-(p-Substit...
Introduction presentationmod
1. Citrullination of peptides
Citrulline – non-proteinogenic amino acid found in most of organisms (in free
form or in proteins and peptides)
Produced in free form from Arginine and less from Glutamate and Aspartate
In peptide is a modification of arginine by PAD-enzymes
Citrullination of proteins is marker of several diseases, including rheumatoid
arthritis
2. Aims
Develop robust and fast method for identification of Citrulline in synthetic peptides
Investigate specific properties of citrulline under positive and negative ionization
Develop peptide structure for most pronounced characteristic features representation
Optimize method for natural peptides and proteins
3. Done so far
Synthesis of sample peptides(???)
Comprehensive method development for positive ionization (Arnold)
Comparison of various peptides for ionization and structural properties, including phase-
dependent analysis (Arnold)
Positive and negative ionization experiments
Initial comparison of patterns between various substituted and non-substituted species in positive
and negative mode
4. Sample spectra (format optimized by Arnold)
292.2320.3
342.4
360.3 413.4 434.3
476.3
487.3
530.3
570.4 627.4
644.4
661.4
686.4703.4
812.5
829.5
846.5
871.5
889.4
+MS2(888.5)
CA = 0.7 V
0.00
0.25
0.50
0.75
1.00
1.25
1.50
4x10
Intens.
300 400 500 600 700 800 900 m/z
Ac-GGYRARPA-NH21+
a3 b3
y3
y4 b4¤
° -H2O
* -NH3
¤ -NH=C=NH
b4
b5*
b6¤
b6¤*
b6¤**
b6b6*
?
b5¤°*
*
¤
¤*
¤**
**
854.5
?
ions providing useful sequential info are underlined1
ions giving neutral loss of -NH=C=NH are highlighted
with blue
