Insertion of organometallic moieties into peptides and peptide nucleic acids using alternative “click” strategies

Abstract

Application of alternative “click” strategies (metal-free photoclick and one-pot click) to cymantrene and ferrocene derivatives yielded novel metal-containing conjugates.

Bioorthogonal Conjugation of Transition Organometallic Complexes to Peptides and Proteins: Strategies and Applications

“…Structures of isolated compounds after their reaction with NLS‐tetrazole and/or PNA‐tetrazole. Adapted from ref …”

“…Gasser and co-workers tried a metal-free 1,3-dipolar cycloaddition between a nitrile imine generated by mild photoactivation of a tetrazole, and an alkene (Scheme 8), [64] coined photoclick, to append two organometallic probes, namely IR-active cymantrene and redox-active ferrocene to molecules with biological activities, to extend their properties. [65] Scheme 8. Principle of photoclick 1,3-dipolar cycloaddition.…”

“…[67] They introduced the tetrazole moiety into the peptide or the PNA sequence by SPPS using acid 31 to yield orthogonal partners NLStetrazole and PNA-tetrazole (Figure 6). [65] These compounds were then reacted with maleimide-modified cymantrene 32 and/or ferrocene 33 upon 302 nm light irradiation at room temperature. It appeared that cymantrene was not the optimal organometallic candidate since the main product of the photoclick cycloaddition with NLS-tetrazole was the by-product 34 arising from hydrolysis of the cycloadduct and concomitant decomposition of Mn(CO) 3 moiety, known to be unstable upon light irradiation.…”

“…They investigated the labelling of a tetrapeptide derivative known as nuclear localization signal (NLS), able to target cell nucleus and a PNA sequence, described as antisense agent inhibiting hepatitis B virus reverse transcription . They introduced the tetrazole moiety into the peptide or the PNA sequence by SPPS using acid 31 to yield orthogonal partners NLS‐tetrazole and PNA‐tetrazole (Figure ) . These compounds were then reacted with maleimide‐modified cymantrene 32 and/or ferrocene 33 upon 302 nm light irradiation at room temperature.…”

‘Clickable’ cyclopentadienyl iron carbonyl complexes for bioorthogonal conjugation of mid‐infrared labels to a model protein and PAMAM dendrimer

“…Alkyne‐containing peptide nucleic acids were labelled with azido‐modified dipicolylamine/amide rhenium tricarbonyl or 99 m‐technetium tricarbonyl moieties for radiotherapeutic purposes . Other representative examples dealt with the labelling of peptides/proteins with bipyridyl rhenium tricarbonyl luminescent labels, and cymantrene entity as IR probe …”