A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

Abstract

Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific double-modification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes.

N-terminal cysteine as minimalistic handle for dual, site-selective bioconjugation: application to an anti-HER2 affibody reveals synergy of two conjugated drugs

“…28 It involves a transthioesterification between a thioester and the NCys thiol, to form a transient intermediate that rearranges via an S-to-N acyl shift. This approach requires the preparation of thioester-functionalized cargos, and has been employed to generate site-selective protein mono-conjugates, [29][30][31] as well as dual conjugates on short peptides, 32,33 via subsequent thiol-Michael addition with a maleimide moiety. Recently, Gao and co-workers reported a more sophisticated 2-step dual conjugation strategy that requires a N-terminal "CIS" (Cys-Ile-Ser) tag in the target protein.…”