Solid-phase fluorescent BODIPY–peptide synthesis via in situ dipyrrin construction. Issue 41 (29th September 2020)

• Record Type: Journal Article
• Authors: Wu, Yue; Tam, Wing-Sze; Chau, Ho-Fai; Kaur, Simranjeet; Thor, Waygen; Aik, Wei Shen; Chan, Wai-Lun; Zweckstetter, Markus; Wong, Ka-Leung
• Is Part Of: Chemical science. Volume 11:Issue 41(2020)
• Page Start: 11266
• Page End: 11273
• Publication Date: 2020-09-29
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc04849f
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Solid-phase fluorescent BODIPY–peptide synthesis via in situ dipyrrin construction offers an efficient fluorescent peptide synthetic platform for multifaceted biomedical applications. Abstract : Traditional fluorescent peptide chemical syntheses hinge on the use of limited fluorescent/dye-taggable unnatural amino acids and entail multiple costly purifications. Here we describe a facile and efficient protocol for in situ construction of dipyrrins on the N-terminus with 20 natural and five unnatural amino acids and the lysine's side chain of selected peptides/peptide drugs through Fmoc-based solid-phase peptide synthesis. The new strategy enables the direct formation of boron–dipyrromethene (BODIPY)–peptide conjugates from simple aldehyde and pyrrole derivatives without pre-functionalization, and only requires a single-time chromatographic purification at the final stage. As a model study, synthesized EBNA1-targeting BODIPY1 –Pep4 demonstrates intact selectivity in vitro, responsive fluorescence enhancement, and higher light cytotoxicity due to the photo-generation of cytotoxic singlet oxygen. This work offers a novel practical synthetic platform for fluorescent peptides for multifaceted biomedical applications.