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  3. A Molecular Logic Gate for Developing "AND" Logic Probes and the Application in Hepatopathy Differentiation

A Molecular Logic Gate for Developing "AND" Logic Probes and the Application in Hepatopathy Differentiation

  • ACS Cent Sci. 2022 Jun 22;8(6):837-844. doi: 10.1021/acscentsci.2c00387.
Mengqi Chen 1,  Chunhong Wang 1,  Zexuan Ding 1,  Hao Wang 2,  Yu Wang 3,  Zhibo Liu 1 4
Affiliations

Affiliations

  • 1 Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • 2 Department of Radiation Oncology, Peking University Third Hospital, 49 North Garden Road, Beijing 100191, China.
  • 3 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
  • 4 Peking University-Tsinghua University Center for Life Sciences, Peking University, Beijing 100871, China.
PMID: 35756368 DOI: 10.1021/acscentsci.2c00387
Abstract

Accurate diagnosis and therapy are challenging because most diseases lack a single biomarker that distinguishes them from Other disorders. A solution would enhance targeting accuracy by using AND-gated combinations of two disease-associated stimuli. Here, we report a novel "AND" molecular logic gate, enabling a double-controlled release of intact Functional Molecules. Benefiting from a significant difference in intramolecular cyclization rate, cargo release occurs notably faster with the presence of both stimuli. According to this finding, several AND logic probes have been developed that respond to a broad scope of stimuli and show remarkably improved signal-to-background contrast compared to those of monoresponsive probes. In addition, an AND logic probe that is responsive to Monoamine Oxidase (MAO) and leucine Aminopeptidase (LAP) has been constructed for hepatopathy diagnosis. It works efficiently in living cells and mouse models. Of note, this probe can successfully differentiate cirrhotic from hepatitis B by testing the blood samples from patients.

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