Mild and Selective Mono-Iodination of Unprotected Peptides as Initial Step for the Synthesis of Bioimaging Probes

Abstract

Chemoselective functionalization of peptides and proteins to selectively introduce residues for detection, capture, or specific derivatization is of high interest to the synthetic community. Here we report a new method for the mild and effective mono-iodination of tyrosine residues in fully unprotected peptides. This method is highly chemoselective and compatible with a wide variety of functional groups. The introduced iodine can subsequently serve as a handle for further functionalization such as introduction of fluorescent dyes and thus be used for chemoselective labeling of isolated peptides.

Transition-Metal-Free Site-Selective γ-C(sp2)–H Monoiodination of Arenes Directed by an Aliphatic Keto Group

“…Aryl iodine is a class of important compounds that can be widely used as clinical drugs, agrochemicals, bioimaging probes, imaging reagents, and highly valuable building blocks in organic synthesis . Therefore, the introduction of iodine atoms on aromatic compounds is a prolonged research topic, and numerous synthetic methods have been explored to date.…”

Fibril Structure Demonstrates the Role of Iodine Labelling on a Pentapeptide Self‐Assembly

“…[13] Beside this methodological applications, iodination has recently received growing interest in nanomaterials science [14][15][16][17] and supramolecular chemistry [18][19][20] as minimal, yet impactful, single-point mutation for small molecules such as peptides. [21,22] This interest arose from the ability of a covalently bonded iodine atom to engage in diverse noncovalent interactions as both Lewis base and Lewis acid. Indeed, its polarizability results in an intrinsic amphoteric behaviour, which allows it to simultaneously engage in both hydrogen (HB) and halogen bonds (XB), according to the surrounding chemical environment.…”

“…Beside this methodological applications, iodination has recently received growing interest in nanomaterials science [14–17] and supramolecular chemistry [18–20] as minimal, yet impactful, single‐point mutation for small molecules such as peptides [21,22] . This interest arose from the ability of a covalently bonded iodine atom to engage in diverse noncovalent interactions as both Lewis base and Lewis acid.…”

Iodinated Diketopiperazines: Synthesis and Biological Evaluation of Iodinated Analogues of Cyclo(L‐Tyrosine‐L‐Tyrosine) Peptides

“…Therefore, halogenated aromatic amino acids represent an important class of building blocks, which have been utilized for various applications. [10][11][12][13] The halogenated tyrosine has been implicated for the structural stabilization of the peptide secondary structure. [14][15][16] The synthetic incorporation of iodine in the tyrosine side chain has been used as a protein labelling technique for its structural and functional studies.…”

“…Halo‐arenes frequently occur in pharmaceuticals and agrochemicals as essential functional molecule [9] (Scheme 1B). Therefore, halogenated aromatic amino acids represent an important class of building blocks, which have been utilized for various applications [10–13] . The halogenated tyrosine has been implicated for the structural stabilization of the peptide secondary structure [14–16] .…”