Synthesis and application of poly(phenylene ethynylene)s for bioconjugation: a conjugated polymer-based fluorogenic probe for proteases.

TitleSynthesis and application of poly(phenylene ethynylene)s for bioconjugation: a conjugated polymer-based fluorogenic probe for proteases.
Publication TypeJournal Article
Year of Publication2005
AuthorsWosnick, JH, Mello, CM, Swager, TM
JournalJournal of the American Chemical Society
Volume127
Pagination3400–5
Date Publishedmar
ISSN0002-7863
KeywordsBiosensing Techniques, Biosensing Techniques: methods, Dinitrobenzenes, Dinitrobenzenes: chemistry, Fluorescence, Fluorescent Dyes, Fluorescent Dyes: chemistry, Kinetics, Osmolar Concentration, Peptide Hydrolases, Peptide Hydrolases: analysis, Peptide Hydrolases: chemistry, Polymers, Polymers: chemical synthesis, Polymers: chemistry, Spectrometry, Surface-Active Agents, Surface-Active Agents: chemistry, Trypsin, Trypsin: analysis, Trypsin: chemistry
Abstract

A set of carboxylate-functionalized poly(phenylene ethynylene)s (PPEs) has been synthesized in which the carboxylic acid groups are separated from the polymer backbone by oligo(ethylene glycol) spacer units. These polymers are soluble in water and organic solvents and have photophysical properties that are sensitive to solvent conditions, with high salt content and the absence of surfactant promoting the formation of aggregates of relatively low quantum yield and long fluorescence lifetime. Quenching of these materials by the dinitrophenyl (DNP) chromophore (K(SV) approximately 10(4)) is also highly solvent-dependent. The presence of carboxylate groups far from the polymer backbone appended to each repeating unit allows for the postpolymerization modification of these PPEs with peptides by methods analogous to those described for carboxylate-functionalized small-molecule dyes. Covalent attachment of the fluorescence-quenching 14-mer Lys(DNP)-GPLGMRGLGGGGK to the PPE results in a nonemissive substrate whose fluorescence is restored upon treatment with trypsin. The rate of fluorescence turn-on in this case is increased 3-fold by the presence of surfactant, though the actual rate of peptide hydrolysis remains the same. A small-molecule mimic of the polymer-peptide system shows a smaller fluorescence enhancement upon treatment with trypsin, illustrating the value of polymer-based amplification in this sensory scheme.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/15755158
DOI10.1021/ja043134b