Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

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外文摘要：Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical research.Aminopeptidase N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting it.In this study,a novel quaternity design strategy for APN theranostic probe was developed.This proposed strategy utilizes advanced machine learning and molecular dynamics simula-tions,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments.Through this strategy,a unique"Off-On"theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restora-tion,relying on conformation-induced effects and solvent restriction.Differ from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imag-ing.The fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

外文关键词：

Theranostic probeArtificial intelligenceConformational restrictionFluorescence restorationDesign strategy

作者：

Yingli Zhu、Jie Qian、Kunqian Yu、Jing Hou、Yeshuo Ma、Fei Chen、Jie Dong、Wenbin Zeng

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作者单位：

Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410083,China

National Engineering Research Center of Rice and Byproduct Deep Processing,School of Food Science and Engineering,Central South University of Forestry and Technology,Changsha 410004,China

State Key Laboratory of Drug Research,Drug Discovery and Design Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

Department of Geriatrics,Third Xiangya Hospital,Central South University,Changsha 410013,China

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基金：

国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Science and Technology Foundation of Hunan ProvinceScience and Technology Foundation of Hunan ProvinceInnovation Fund for Postgraduate Students of Central South UniversityInnovation Fund for Postgraduate Students of Central South UniversityNMR measurements by the Modern Analysis and Testing Center of CSU

项目编号：

82272067819743862210712322003078M-06962022JJ800522022JJ406562021zzts09802023ZZTS0842

出版年：

2024

DOI：

10.1016/j.cclet.2023.108948

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCD

影响因子：0.771

ISSN：1001-8417

年,卷(期)：2024.35(2)

参考文献量54