Solid-Phase Peptide Macrocyclization and Multifunctionalization via Dipyrrin Construction

Angew Chem Int Ed Engl. 2021 Sep 6;60(37):20301-20307. doi: 10.1002/anie.202108885. Epub 2021 Aug 6.

Abstract

We introduce a new and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid-phase peptide macrocyclization via dipyrrin construction, with full scope of proteinogenic amino acids and different ring sizes. Various bicyclic peptides can be created by dipyrrin-based crosslinking and double dipyrrin-ring formation. The embedded dipyrrin can be either transformed to fluorescent BODIPY and then utilized as cancer-selective targeted protein imaging probe in vitro, or directly employed as a selective metal sensor in aqueous media. This work provides a valuable addition to the peptide macrocyclization toolbox, and a blueprint for the development of multifunctional dipyrrin linkers in cyclopeptides for a wide range of potential bioapplications.

Keywords: dipyrrin; fluorescent cyclic peptides; solid-phase peptide synthesis; zinc(II) sensing; αvβ3 imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / chemistry*
  • Coordination Complexes / chemistry*
  • Macrocyclic Compounds / chemistry*
  • Molecular Conformation
  • Peptides / chemistry*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Coordination Complexes
  • Macrocyclic Compounds
  • Peptides