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Reactivity and gas‐phase acidity determinations of small peptide ions consisting of 11 to 14 amino acid residues
Author(s) -
Carr Scott R.,
Cassady Carolyn J.
Publication year - 1997
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(199709)32:9<959::aid-jms552>3.0.co;2-5
Subject(s) - chemistry , deprotonation , protonation , electrospray ionization , medicinal chemistry , stereochemistry , ion , crystallography , organic chemistry
Small peptides ions consisting of a comparable number of amino acid residues but varying in composition and sequence were allowed to undergo gas‐phase deprotonation reactions. These multiply protonated ions were generated by electrospray ionization and analyzed in a Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometer. The peptides studied contain 11–14 amino acid residues and included adrenocorticotropic hormone (ACTH) fragment (11–24), fibrinopeptide B (human), gastrin I fragment (1–13) (human), renin substrate tetradecapeptide (horse), somatostatin, substance P and tyrosine protein kinase. Rate constants were determined for the deprotonation reactions of the peptide ions with a series of reference compounds of known gas‐phase basicities ranging from 190.0 to 232.6 kcal mol ‐1 . From these values, apparent gas‐phase acidities ( GA app ) were assigned to [M+ n H] n + ( n ⩾2), of each peptide. All of the multiply charged peptide ions were sequentially deprotonated to the +1 charge state by ion–molecule reactions. The GA app s ranged from 193.3 kcal mol ‐1 (for [M+4H] 4+ of renin substrate, the ion most readily deprotonated) to >232.6 kcal mol ‐1 (for [M+2H] 2+ of ACTH (11–24), the ion most difficult to deprotonate). The proximity of intrinsically basic sites (and therefore potential protonation sites) has an effect on the observed deprotonation rates. Ions experiencing Coulomb repulsion resulting from adjacent protonation sites often show more facile deprotonation. However, the intrinsic basicity of a protonation site also plays a role in determining the ease of deprotonation. As a result, some lower charge state peptide ions deprotonate more readily than other peptides with higher charges but with more basic protonation sites. In addition, conformation and the influence of intramolecular hydrogen bonding may affect the reactivity of some peptide ions. Also observed was non‐linear kinetic behavior that indicates multiple isomers at certain charge states for some peptides, e.g. [M+ n H] n + , ( n =2 and 3) for ACTH 11–24 and [M+3H] 3+ for somatostatin. © 1997 by John Wiley & Sons, Ltd.