Linked Life Data

19947633

Source:http://linkedlifedata.com/resource/pubmed/id/19947633

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2009-12-23
pubmed:abstractText
The chemistry of peptide fragmentation by collision-induced dissociation (CID) is currently being reviewed, as a result of observations that the amino acid sequence of peptide fragments can change upon activation. This rearrangement mechanism is thought to be due to a head-to-tail cyclization reaction, where the N-terminal and C-terminal part of the fragment are fused into a macrocycle (= cyclic peptide) structure, thus "losing" the memory of the original sequence. We present a comprehensive study for a series of b fragment ions, from b(2) to b(8), based on the simplest amino acid residue glycine, to investigate the effect of peptide chain length on the appearance of macrocycle fragment structures. The CID product ions are structurally characterized with a range of gas-phase techniques, including isotope labeling, infrared photodissociation spectroscopy, gas-phase hydrogen/deuterium exchange (using CH(3)OD), and computational structure approaches. The combined insights from these results yield compelling evidence that smaller b(n) fragments (n = 2, 3) exclusively adopt oxazolone-type structures, whereas a mixture of oxazolone and macrocycle b fragment structures are formed for midsized b(n) fragments, where n = 4-7. As each of these chemical structures exchanges at different rates, it is possible to approximate the relative abundances using kinetic fits to the H/D exchange data. Under the conditions used here, the "slow"-exchanging macrocycle structure represents approximately 30% of the b ion population for b(6)-b(7), while the "fast"-exchanging oxazolone structure represents the remainder (70%). Intriguingly, for b(8) only the macrocycle structure is identified, which is also consistent with the "slow" kinetic rate in the HDX results. In a control experiment, a protonated cyclic peptide with 6 amino acid residues, cyclo(Gln-Trp-Phe-Gly-Leu-Met), is confirmed not to adopt an oxazolone structure, even upon collisional activation. These results demonstrate that in some cases larger macrocycle structures are surprisingly stable. While more studies are required to establish the general propensity for cyclization in b fragments, the implications from this study are troubling in terms of faulty sequence identification.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18272-82
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effect of peptide fragment size on the propensity of cyclization in collision-induced dissociation: oligoglycine b(2)-b(8).
pubmed:affiliation
Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't