TY  - JOUR
AU  - Wu, Yue
AU  - Tam, Wing-Sze
AU  - Chau, Ho-Fai
AU  - Kaur, Simranjeet
AU  - Thor, Waygen
AU  - Aik, Wei Shen
AU  - Chan, Wai Lun
AU  - Zweckstetter, Markus
AU  - Wong, Ka-Leung
TI  - Solid-phase fluorescent BODIPY–peptide synthesis via in situ dipyrrin construction
JO  - Chemical science
VL  - 11
IS  - 41
SN  - 2041-6539
CY  - Cambridge
PB  - RSC
M1  - DZNE-2021-00085
SP  - 11266 - 11273
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34094367
C2  - pmc:PMC8162834
DO  - DOI:10.1039/D0SC04849F
UR  - https://pub.dzne.de/record/154224
ER  -