Selective Functionalization of Peptides with Reactive Fragment Ions

Area of Science:

• Mass spectrometry
• Inorganic chemistry
• Peptide chemistry

Background:

• Selective modification of peptides is crucial for bioconjugate development.
• Gas-phase inorganic fragment ions offer unique reactivity for chemical synthesis.

Purpose of the Study:

• To demonstrate selective binding of inorganic fragment ions to peptides.
• To control bioconjugate formation using mass-selected deposition.
• To characterize the reaction products and mechanisms.

Main Methods:

• Generation of closo-dodecaborate fragment ions ([B12I11]- and [B12I8S(CN)]-) via collision-induced dissociation.
• Sequential mass-selected deposition of ions onto dipeptides (leucyl proline, phenylalanyl proline, tyrosyl proline).
• Structural characterization of products using electrospray ionization tandem mass spectrometry and deuterium labeling.

Main Results:

• The highly reactive [B12I11]- ion selectively binds to hydrophobic N-terminal side chains, forming non-thermochemically preferred isomers.
• The less reactive [B12I8S(CN)]- ion reacts with polar functional groups, yielding primarily thermochemically preferred products.
• Demonstrated control over bioconjugate formation through selective ion-peptide interactions.

Conclusions:

• Gas-phase inorganic fragment ions can serve as unconventional building blocks for selective bioconjugation.
• Reaction selectivity is influenced by ion reactivity and peptide functional groups.
• This approach enables controlled synthesis of novel peptide-based materials.