Protein recognition by a pattern-generating fluorescent molecular probe

Abstract

Fluorescent molecular probes have become valuable tools in protein research; however, the current methods for using these probes are less suitable for analysing specific populations of proteins in their native environment. In this study, we address this gap by developing a unimolecular fluorescent probe that combines the properties of small-molecule-based probes and cross-reactive sensor arrays (the so-called chemical 'noses/tongues'). On the one hand, the probe can detect different proteins by generating unique identification (ID) patterns, akin to cross-reactive arrays. On the other hand, its unimolecular scaffold and selective binding enable this ID-generating probe to identify combinations of specific protein families within complex mixtures and to discriminate among isoforms in living cells, where macroscopic arrays cannot access. The ability to recycle the molecular device and use it to track several binding interactions simultaneously further demonstrates how this approach could expand the fluorescent toolbox currently used to detect and image proteins.

Decorating bacteria with self-assembled synthetic receptors

“…Figure 1 shows the design and operating principles of a synthetic receptor system that fulfills these requirements. This design borrows principles from our previous studies in which we demonstrated the possibility of generating ODN-small-molecule conjugates that can non-covalently bind to several different proteins 21,22 . We hypothesized that if one of the protein targets for such synthetic protein binders would be located on the cell surface, their regulatory effect 21 could be extended from the protein level to the cellular level.…”

“…In recent years, considerable attention has been devoted to developing protein binders based on oligodeoxynucleotide (ODN)-small-molecule conjugates [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] that, similar to CSPs, can respond to external stimuli and undergo dynamic structural changes that enable them to reversibly interact with proteins and regulate their functions [11][12][13][14][15][16][17][18][19][20][21] . We have recently developed protein binders based on ODN-small-molecule conjugates [21][22][23] and have shown that such binders can be designed to reversibly interact with different proteins 21,22 and even mediate unnatural protein-protein communication processes 21 . Parallel to these efforts, much progress has been made in the ability to modify cell surfaces with synthetic agents that bear unique functionalities [28][29][30][31] .…”

Two‐Photon‐Induced CO‐Releasing Molecules as Molecular Logic Systems in Solution, Polymers, and Cells

“…Herein, we propose to also analyze 2PA‐induced CO release as a new form of molecular logic gates. The optically activated, cancer‐targeted CORMs presented in this work display excellent properties as molecular logic devices since they can process concomitantly electromagnetic, chemical, and environmental information …”

“…[27] Herein, we propose to also analyze 2PA-induced CO release as an ew form of molecular logic gates.T he optically activated, cancer-targeted CORMs presented in this work display excellent properties as molecular logic devices since they can process concomitantly electromagnetic, chemical, and environmental information. [28][29][30] Herein, photoCORMsc ompounds 1-2 (Scheme1)c ombine a [Mn I (CO) 3 ]C O-rich fragment with ap otentially emissive dipicolylamine-1,8-naphthalimide ligand,w hile 2 also integrates a biotin tether.T he turn-on fluorescent chromophore 1,8-naphthalimide has al arge2 PA cross-section [31][32][33][34] and can be excited between l exc = 600-950 nm. [35][36][37][38] Biotin is required to sustain the natural growth of eukaryotic cells.…”

Array‐basierte Sensorik mit der “chemischen Nase” in der Diagnostik und Wirkstoffentdeckung

“…Kürzlich berichteten Margulies et al. über eine elegante, mehrteilige Fluoreszenzsonde mit drei fluoreszierenden proteinbindenden Einheiten: einer DNA‐Aptamer‐Haarnadel und zwei zusätzlichen Proteinerkennungsstellen auf Basis niedermolekularer Verbindungen (Abbildung ) . Ausgewählt wurden die Proteinerkennungsstellen anhand bekannter, nicht‐spezifischer bindender Wechselwirkungen mit krankheitsassoziierten Proteinfamilien, wie Glutathion‐S‐Transferasen (GSTs), Matrix‐Metalloproteasen (MMPs) und thrombozytären Wachstumsfaktoren (PDGFs).…”