Referenced in: none

Automatically associated channels: Kv10.1

Title: Site-preferential dissociation of peptides with active chemical modification for improving fragment ion detection.

Authors: Pamela Ann C Diego, Bekim Bajrami, Hui Jiang, Yu Shi, José A Gascón, Xudong Yao

Journal, date & volume: Anal. Chem., 2010 Jan 1 , 82, 23-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19904916

Abstract
Multiple reaction monitoring tandem mass spectrometry becomes an important strategy for measuring protein targets in complex biomatrixes. Active chemical modification of peptides like phenylthiocarbamoylation has unique potential for improving the measurement. This potential is enabled by active participation of a modifying group in site-preferential dissociation of modified peptides, which produces certain fragment ions at very high yields and in a sequence-independent manner. In this work, a novel combination of energy-resolved mass spectrometry with substituent effect investigation is used to analyze important factors that control the specificity of the site-preferential dissociation of phenylthiocarbamoyl peptides. On the basis of the linear correlation between collision energy and the Hammett constant as well as computational studies, it is found that the initial enhanced capture of a mobile proton and the subsequent, site-directed intramolecular proton transfer are important to the high yields (approximately 70-90%) for producing two types of fragment ions of phenylthiocarbamoyl peptides: the modified b(1) ion and the complementary y(n-1) ion. This understanding will help the design of new modification reagents. When integrated with the throughput and the signal-enhancing potential of peptide modification, active chemical modification of peptides will significantly advance mass spectrometry-based, targeted proteome analysis.