Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [18F]AlF-Affibody Conjugates

Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide–thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions.

Chemiluminescent read-out of para-fluoro-thiol reaction events

We exploit the fluoride that is released via the para-fluoro-thiol reaction (PFTR) to cleave silyl ethers, turning the PFTR into an effective self-reporting chemiluminescence (CL) probe.

A green carbon dots-based fluorescent sensor for selective and visual detection of nitrite triggered by the nitrite–thiol reaction

Selective and visual detection of nitrite is realized through the inner-filter effect triggered by the nitrite–thiol reaction based on green carbon dots.

A kinetic study on the para-fluoro-thiol reaction in view of its use in materials design

A detailed kinetic study on the para-fluoro-thiol reaction (PFTR) using experimental analysis and kinetic Monte Carlo modeling is introduced, covering the difference in reactivity of a selected variety of structurally different thiols, uniquely including polymeric thiols.

The para-fluoro-thiol reaction as an efficient tool in polymer chemistry

The current literature describing the application of the para-fluoro–thiol reaction in the realm of macromolecular chemistry and the future of this coupling strategy are discussed.

The para-fluoro-thiol reaction as a powerful tool for precision network synthesis

We introduce the regioselective para-fluoro-thiol reaction (PFTR) as a novel strategy for precision network formation evidenced by XPS and ToF-SIMS.