Recently, Zhibo Liu group from the College of Chemistry and Molecular Engineering, Peking University published an article entitled “A Molecular Logic Gate for Developing ‘AND’ Logic Probes and the Application in Hepatopathy Differentiation” in ACS Central Science. This study reported a novel “AND” molecular logic gate, enabling a double-controlled release of intact functional molecules. Based on this finding, an AND logic probe with higher imaging specificity was constructed and successfully applied to achieve accurate hepatopathy differentiation in mouse and human serum samples.
Fig. 1 AND logic probe applied to accurate hepatopathy differentiation.
Accurate diagnosis and therapy are challenging because most diseases lack a single biomarker that distinguishes them from other disorders. As a result, single-triggered strategies have difficulties in the accurate recognition of diseases. Inspired by the dual targeting strategy guided by a radio-imaging probe (Nature, 2020, 579, 421-426), Zhibo Liu group further developed a novel AND logic controlled release system.
Fig. 2 General design of the AND molecular logic gate.
First, the authors successfully screened two kinds of AND molecular logic triggers with Bicine and Dien as skeletons. After the double response, the rapid intramolecular cyclization reaction and the release of intact functional molecules can occur, and the release rate was up to 100 times that of the single response. Furthermore, the authors extended the universality of the system, successfully coupling a variety of triggering moieties and functional molecules. Subsequently, an AND logic probe responsive to monoamine oxidase (MAO) and leucine aminopeptidase (LAP) was constructed, which had a lower background signal in cell imaging than monoresponsive probes. Moreover, the probe can reduce false-positive signals in serum testing, and was successfully applied to achieve accurate hepatopathy differentiation in mouse and human serum samples. In conclusion, this work has developed a novel AND logic controlled release system, and is expected to lead to a key breakthrough in precise diagnosis and treatment of diseases.
Mengqi Chen is the first author of this paper. Prof. Zhibo Liu is the corresponding author. This research was funded by the National Natural Science Foundation of China, the Ministry of Science and Technology of the People's Republic of China, the Beijing Municipal Natural Science Foundation, the Special Foundation of Beijing Municipal Education Commission, Peking University Ge Li and Ning Zhao Life Science Research Fund for Young Scientists, the Peking-Tsinghua Center for Life Sciences and the Beijing National Laboratory for Molecular Sciences.
Original link for the paper: https://doi.org/10.1021/acscentsci.2c00387.
