Cyanine Masking: A Strategy to Test Functional Group Effects on Antibody Conjugate Targeting

Thapaliya, Ek Raj; Usama, Syed Muhammad; Patel, Nimit L.; Feng, Yang; Kalen, Joseph D.; Croix, Brad St.; Schnermann, Martin J.

doi:10.26434/chemrxiv-2022-3j2ls

Cited by 1 publication

(1 citation statement)

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“…With this goal in mind, we designed FNIR-Tag-766 (Figure 4A), which contains both trimethylpropyl ammonium indolenine substituents and a N-trimethylpropyl-ammonium-N-butyl-sulfonate tertiary amide, which we used previously, at the 2-position of the C4′ aryl ring. 51 FNIR-Tag-766 was synthesized, as shown in Figure 4A. Starting from aryl pyridine 5, the key hindered tertiary amide 6 was accessed by the way of an acyl fluoride intermediate.…”

Section: Imagingmentioning

confidence: 99%

Method To Diversify Cyanine Chromophore Functionality Enables Improved Biomolecule Tracking and Intracellular Imaging

Usama

Marker

et al. 2023

J. Am. Chem. Soc.

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Heptamethine indocyanines are invaluable probes for near-infrared (NIR) imaging. Despite broad use, there are only a few synthetic methods to assemble these molecules, and each has significant limitations. Here, we report the use of pyridinium benzoxazole (PyBox) salts as heptamethine indocyanine precursors. This method is high yielding, simple to implement, and provides access to previously unknown chromophore functionality. We applied this method to create molecules to address two outstanding objectives in NIR fluorescence imaging. First, we used an iterative approach to develop molecules for protein-targeted tumor imaging. When compared to common NIR fluorophores, the optimized probe increases the tumor specificity of monoclonal antibody (mAb) and nanobody conjugates. Second, we developed cyclizing heptamethine indocyanines with the goal of improving cellular uptake and fluorogenic properties. By modifying both the electrophilic and nucleophilic components, we demonstrate that the solvent sensitivity of the ring-open/ring-closed equilibrium can be modified over a wide range. We then show that a chloroalkane derivative of a compound with tuned cyclization properties undergoes particularly efficient no-wash live cell imaging using organelle-targeted HaloTag self-labeling proteins. Overall, the chemistry reported here broadens the scope of accessible chromophore functionality, and, in turn, enables the discovery of NIR probes with promising properties for advanced imaging applications.

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Section: Imagingmentioning

confidence: 99%