# Cyclic Peptide–Polymer Conjugate Characterization Using 193 nm Ultraviolet Photodissociation Tandem Mass Spectrometry

## TL;DR

This paper explores using advanced mass spectrometry techniques to analyze cyclic peptide-polymer conjugates, which are complex but promising for biomedical applications.

## Contribution

The study demonstrates the effectiveness of 193 nm UVPD for characterizing both cyclic peptides and their conjugated polymers in a single experiment.

## Key findings

- UVPD effectively produced complete cyclic peptide fragmentation and polymer fragmentation via specific pathways.
- ECD and IRMPD provided complementary data for analyzing conjugated systems.
- ECD was less effective for cyclic peptides due to sequence scrambling but useful for conjugated side chains.

## Abstract

Cyclic peptide–polymer conjugates offer a unique
biocompatible
system with many advantages but come at the cost of being analytically
challenging. Developing further analytical techniques of complex polymer-conjugate
systems is key to understanding synthetic and medicinal properties.
In this contribution, a synthetic cyclic peptide–polymer conjugate
is analyzed using electron capture dissociation (ECD), infrared multiphoton
absorption dissociation (IRMPD), and 193 nm ultraviolet photodissociation
(UVPD) on the same mass spectrometry system. IRMPD and UVPD were shown
to effectively characterize unconjugated cyclic peptide species. ECD
was less informative during cyclic peptide analysis due to the production
of multiple sequence scrambling fragments and radical side chain losses.
ECD was shown to produce extensive fragmentation and enable the characterization
of conjugated side chains of cyclic species. ECD and IRMPD thus provided
complementary data, enabling the target analysis of conjugated systems.
UVPD effectively characterized both the cyclic peptide and the conjugating
polymer in one experiment, being able to produce complete cyclic peptide
fragmentation via b/y fragment pathways
and polymer fragmentation via a/x poly­(2-ethyl-2-oxazoline) fragment pathways.