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Title: Solid-phase approaches for labelling targeting peptides with far-red emitting coumarin fluorophores
Author: Rovira, Anna
Gandioso, Albert
Goñalons, Marina
Galindo Muñoz, Alex
Massaguer i Vall-llovera, Anna
Bosch, Manel
Marchán Sancho, Vicente
Keywords: Síntesi de pèptids
Cèl·lules canceroses
Peptide synthesis
Cancer cells
Issue Date: 10-Jan-2019
Publisher: American Chemical Society
Abstract: Fluorophores based on organic molecules hold great potential for ligand-targeted imaging applications, particularly those operating in the optical window in biological tissues. In this work, we have developed three straightforward solid-phase approaches based on amide-bond formation or a Cu(I)-catalyzed azide-alkyne click (CuAAC) reaction for labeling an octreotide peptide with far-red emitting coumarin-based COUPY dyes. First, the conjugatable versions of COUPY fluorophores incorporating the required functional groups (e.g., carboxylic acid, azide, or alkyne) were synthesized and characterized. All of them were found fully compatible with Fmoc/tBu solid-phase peptide synthesis, which allowed for the labeling of octreotide either through amide-bond formation or by CuAAC reaction. A near quantitative conversion was obtained after only 1 h of reaction at RT when using CuSO4 and sodium ascorbate independently of the click chemistry approach used (azido-COUPY/alkynyl-peptide resin or alkynyl-COUPY/azido-peptide resin). COUPY-octreotide conjugates were found stable in cell culture medium as well as noncytotoxic in HeLa cells, and their spectroscopic and photophysical properties were found similar to those of their parent coumarin dyes. Finally, the potential bioimaging applications of COUPY-octreotide conjugates were demonstrated by confocal microscopy through the visualization of living HeLa cells overexpressing the somatostatin subtype-2 receptor.
Note: Versió postprint del document publicat a:
It is part of: Journal of Organic Chemistry, 2019, vol. 84, num. 4, p. 1808-1817
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ISSN: 0022-3263
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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