University of Illinois Urbana-Champaign

Design and Optimization of a Dual-input Logic-gated Activatable Probe

Chen, Yibin

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https://hdl.handle.net/2142/133263

Description

Title
Design and Optimization of a Dual-input Logic-gated Activatable Probe
Author(s)
Chen, Yibin
Contributor(s)
Chan, Jefferson
Issue Date
2026-05-13
Keyword(s)
  • Dual-input Logic Gate
  • Carbamate Elimination
  • Oxazolidine Masking
  • Activatable Fluresent Probe
Date of Ingest
2026-05-13T09:30:55-05:00
Abstract
This study presents a dual-input logic-gated, activatable fluorescent probe platform to enhance selective recognition capabilities in complex tumor-associated environments. In the previous design, we employed a ketal structure to mask the ketone group. However, experiments revealed that the system relies on a 1,6-elimination reaction for ketone regeneration during activation, with relatively slow kinetics that potentially limit overall response efficiency. To address the constrained ketone regeneration rate, we structurally optimized the masking strategy. By introducing a carbamate self-elimination structure and coupling it to the ketone regeneration pathway, we designed a masking system based on an oxazolidine moiety. This design leverages the faster kinetics of carbamate elimination to replace the original slow elimination pathway. This helps improve ketone regeneration after activation while keeping the system stable before triggering. Within the optimized platform, two independent triggers are integrated into a single molecular structure, forming a dual-input logic gate mechanism that achieves full activation only when both trigger conditions are simultaneously satisfied. In vitro fluorescence experiments demonstrate that the system remains largely inert under a single trigger signal but exhibits significant fluorescence enhancement under dual-input conditions. Cellular imaging experiments further validate the selective activation capability of the logic gate design within cellular environments. In vivo results demonstrate that, compared to single- trigger systems, the dual-input logic gate structure significantly reduces off-target activation in GSH-rich organs.
Publisher
University of Illinois Urbana-Champaign
Type of Resource
text
Genre of Resource
article
Language
eng
Copyright and License Information
2026 Tom Chen

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