4.5 Review

FT-MS in the de novo top-down sequencing of natural nontryptic peptides

Journal

MASS SPECTROMETRY REVIEWS
Volume 41, Issue 2, Pages 284-313

Publisher

WILEY
DOI: 10.1002/mas.21678

Keywords

de novo sequencing; disulfide bonds; FT‐ ICR; natural peptides; tandem mass spectrometry

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The present review discusses the application of FT-MS for de novo sequencing of natural peptides from various animals. These peptides are bioactive and are used by animals as a weapon against microorganisms and predators. They have potential as drugs of the future generation, as their mechanism of action is different from modern antibiotics. De novo sequencing becomes challenging when the species genome is unavailable and little is known about the peptides. The benefits of FT-MS for top-down peptide sequencing and the difficulties encountered in sequence elucidation are discussed.
The present review covers available results on the application of FT-MS for the de novo sequencing of natural peptides of various animals: cones, bees, snakes, amphibians, scorpions, and so forth. As these peptides are usually bioactive, the animals efficiently use them as a weapon against microorganisms or higher animals including predators. These peptides represent definite interest as drugs of future generations since the mechanism of their activity is completely different in comparison with that of the modern antibiotics. Utilization of those peptides as antibiotics can eliminate the problem of the bacterial resistance development. Sequence elucidation of these bioactive peptides becomes even more challenging when the species genome is not available and little is known about the protein origin and other properties of those peptides in the study. De novo sequencing may be the only option to obtain sequence information. The benefits of FT-MS for the top-down peptide sequencing, the general approaches of the de novxxo sequencing, the difficult cases involving sequence coverage, isobaric and isomeric amino acids, cyclization of short peptides, the presence of posttranslational modifications will be discussed in the review.

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