Abstract
A combination of mass spectrometry and ab initio calculations (MP2/6-31+G(d)//HF/6-31+G(d)) has been used to study the mechanism of C-terminal residue cleavage in gas phase peptide/alkali metal ion complexes. Although previous workers had suggested a mechanism relying on a concerted cleavage of an oxazolidin-5-one intermediate, the present calculations indicate that this pathway has a high barrier and is not competitive. Instead, it appears that the mechanism involves a rearrangement to an anhydride intermediate that fragments to give the observed products. The computational data indicates that this mechanism has a much lower activation energy than a concerted pathway and should be viable. Moreover, compelling evidence for the mechanism is found in experiments involving the lithium complexes of dipeptides. In the proposed mechanism, the two amino acids of a dipeptide are in equivalent positions in the anhydride intermediate (i.e., sequence information is lost) and therefore, fragmentation of either sequence of a dipeptide should give the same result. This was confirmed for eight pairs of dipeptides by collision-induced dissociation (CID) of their lithium complexes in a quadrupole ion trap mass spectrometer. Although the CID spectra are not identical, the yields of the products that would pass through the anhydride intermediate are nearly equivalent, independent of the original sequence. Finally, additional computational work shows that the mechanism does not rely on the presence of a metal and is also viable as a charge-remote fragmentation pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 117-134 |
| Number of pages | 18 |
| Journal | International Journal of Mass Spectrometry |
| Volume | 222 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Jan 1 2003 |
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Keywords
- Anhydride
- Fragmentation
- Lithium
- Pathway
- Peptide
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Spectroscopy
Cite this
The mechanism of C-terminal fragmentations in alkali metal ion complexes of peptides. / Feng, Wan Yong; Gronert, Scott; Fletcher, Kirsten A.; Warres, Abdul; Lebrilla, Carlito B.
In: International Journal of Mass Spectrometry, Vol. 222, No. 1-3, 01.01.2003, p. 117-134.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The mechanism of C-terminal fragmentations in alkali metal ion complexes of peptides
AU - Feng, Wan Yong
AU - Gronert, Scott
AU - Fletcher, Kirsten A.
AU - Warres, Abdul
AU - Lebrilla, Carlito B
PY - 2003/1/1
Y1 - 2003/1/1
N2 - A combination of mass spectrometry and ab initio calculations (MP2/6-31+G(d)//HF/6-31+G(d)) has been used to study the mechanism of C-terminal residue cleavage in gas phase peptide/alkali metal ion complexes. Although previous workers had suggested a mechanism relying on a concerted cleavage of an oxazolidin-5-one intermediate, the present calculations indicate that this pathway has a high barrier and is not competitive. Instead, it appears that the mechanism involves a rearrangement to an anhydride intermediate that fragments to give the observed products. The computational data indicates that this mechanism has a much lower activation energy than a concerted pathway and should be viable. Moreover, compelling evidence for the mechanism is found in experiments involving the lithium complexes of dipeptides. In the proposed mechanism, the two amino acids of a dipeptide are in equivalent positions in the anhydride intermediate (i.e., sequence information is lost) and therefore, fragmentation of either sequence of a dipeptide should give the same result. This was confirmed for eight pairs of dipeptides by collision-induced dissociation (CID) of their lithium complexes in a quadrupole ion trap mass spectrometer. Although the CID spectra are not identical, the yields of the products that would pass through the anhydride intermediate are nearly equivalent, independent of the original sequence. Finally, additional computational work shows that the mechanism does not rely on the presence of a metal and is also viable as a charge-remote fragmentation pathway.
AB - A combination of mass spectrometry and ab initio calculations (MP2/6-31+G(d)//HF/6-31+G(d)) has been used to study the mechanism of C-terminal residue cleavage in gas phase peptide/alkali metal ion complexes. Although previous workers had suggested a mechanism relying on a concerted cleavage of an oxazolidin-5-one intermediate, the present calculations indicate that this pathway has a high barrier and is not competitive. Instead, it appears that the mechanism involves a rearrangement to an anhydride intermediate that fragments to give the observed products. The computational data indicates that this mechanism has a much lower activation energy than a concerted pathway and should be viable. Moreover, compelling evidence for the mechanism is found in experiments involving the lithium complexes of dipeptides. In the proposed mechanism, the two amino acids of a dipeptide are in equivalent positions in the anhydride intermediate (i.e., sequence information is lost) and therefore, fragmentation of either sequence of a dipeptide should give the same result. This was confirmed for eight pairs of dipeptides by collision-induced dissociation (CID) of their lithium complexes in a quadrupole ion trap mass spectrometer. Although the CID spectra are not identical, the yields of the products that would pass through the anhydride intermediate are nearly equivalent, independent of the original sequence. Finally, additional computational work shows that the mechanism does not rely on the presence of a metal and is also viable as a charge-remote fragmentation pathway.
KW - Anhydride
KW - Fragmentation
KW - Lithium
KW - Pathway
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=0037212298&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037212298&partnerID=8YFLogxK
U2 - 10.1016/S1387-3806(02)00958-2
DO - 10.1016/S1387-3806(02)00958-2
M3 - Article
AN - SCOPUS:0037212298
VL - 222
SP - 117
EP - 134
JO - International Journal of Mass Spectrometry
JF - International Journal of Mass Spectrometry
SN - 1387-3806
IS - 1-3
ER -