Tailored photocleavable peptides: fragmentation and neutralization pathways in high vacuum

Abstract

Photocleavable tags (PCTs) have the potential for excellent spatio-temporal control over the release of subunits of complex molecules.

Neutralization of insulin by photocleavage under high vacuum

“…The parent ions and their cleavage products are then analysed by high-resolution time-of-flight mass spectrometry. 16 The data of Fig. 1 show that our model compounds fulfill their design specifications well: the charged leaving groups negLG À and posLG + cleave under H-transfer or homolytically, without resulting in charge transfer between the dissociating partners.…”

“…15 Similar observations were made with peptides, launched by ESI where additionally clean cleavage was confirmed. 16 Here we introduce photocleavable tags with charge-decorated leaving groups for peptides and proteins. They can be removed in an overall non-heterolytic process that reduces the peptide charge stepwise by one unit:…”

“…In contrast to that, earlier studies found that a similarly structured neutral leaving group neuLG cleaves heterolytically for tripeptides and mostly via H-transfer for longer peptides, thereby limiting the applicability for charge reduction by photocleavage to small peptides in the negative ion mode (Scheme 1). 16 In our present work, fluorinated phenols with either a positive tetraalkylammonium (posLG + ) or a negative sulfonate (negLG À ) group are explored as leaving group motifs. 15,16 They are bound to a set of tri-and nonapeptides 1 and 2 (sequences: KAL and KALGALGAL, respectively) shown in Scheme 1, which contain only non-aromatic amino acids to minimize absorption.…”

“…16 In our present work, fluorinated phenols with either a positive tetraalkylammonium (posLG + ) or a negative sulfonate (negLG À ) group are explored as leaving group motifs. 15,16 They are bound to a set of tri-and nonapeptides 1 and 2 (sequences: KAL and KALGALGAL, respectively) shown in Scheme 1, which contain only non-aromatic amino acids to minimize absorption.…”

Matter–wave interference and deflection of tripeptides decorated with fluorinated alkyl chains

“…Our study also shows that future experiments would benefit from cold sources for improved molecule stability and laser ionization detection for improved detection efficiency. Recent progress in ultrafast laser desorption and vacuum ultraviolet photoionization of tryptophan‐rich polypeptides, 22 as well as progress in the neutralization of biomolecular beams prepared by electrospray ionization and photo‐cleavage neutralization, 34,35 are expected to enable research with a wide range of large peptides 23 …”