Abstract
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.
基金项目
国家自然科学基金(82272067)
国家自然科学基金(81974386)
国家自然科学基金(22107123)
国家自然科学基金(22003078)
国家自然科学基金(M-0696)
Science and Technology Foundation of Hunan Province(2022JJ80052)
Science and Technology Foundation of Hunan Province(2022JJ40656)
Innovation Fund for Postgraduate Students of Central South University(2021zzts0980)
Innovation Fund for Postgraduate Students of Central South University(2023ZZTS0842)
NMR measurements by the Modern Analysis and Testing Center of CSU()
维普
万方数据