3 years ago

Environment-Sensitive Turn-On Fluorescent Polyamino Acid: Fingerprinting Protein Populations with Post-Translational Modifications

Environment-Sensitive Turn-On Fluorescent Polyamino Acid: Fingerprinting Protein Populations with Post-Translational Modifications
Shunsuke Tomita, Ryoji Kurita, Sayaka Ishihara
The identification of post-translational modifications (PTMs) in proteins has been of particular interest in the elucidation of human diseases and the improvement of therapeutic proteins. Herein, we report a novel strategy toward the construction of fingerprint-based PTM-sensing systems as an alternative to conventional specific recognition tools. Our strategy is based on poly-l-lysine (PLL) derivatives with two distinct properties suitable to fingerprint-based protein-sensing: (i) a turn-on fluorescent signal upon binding to proteins and (ii) condition-dependent cross-reactivity toward proteins and PTMs. One type of PLL derivative under varying solution properties (pH value and ionic strength) was sufficient to construct a sensing array that produces unique fluorescence fingerprints for structurally similar mammalian albumins with/without a wide variety of chemical modifications corresponding to PTMs. This approach was also applicable for the recognition of deviations in physicochemical properties of proteins as a result of realistic glycation and phosphorylation events. Multivariate analyses of the thus obtained fingerprints successfully identified analytes with 100% accuracy (qualitatively and quantitatively) in all cases. This study thus demonstrates for the first time a fingerprint-based sensing of proteins with/without PTMs using a single, highly accessible, and tunable synthetic polymer, and accordingly offers a powerful platform for simple high-throughput sensing of PTMs in proteins.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b05360

DOI: 10.1021/acsami.7b05360

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