Design and synthesis of peptide-drug conjugates and fluorescent probe based on α-conotoxin ArIBV11L,V16D
10.16438/j.0513-4870.2023-0577
- VernacularTitle:α-芋螺毒素ArIB[V11L,V16D]多肽偶联药物与荧光探针的设计与合成
- Author:
Xin SUN
;
Jiang-nan HU
;
Su-lan LUO
;
Shuai DONG
- Publication Type:Research Article
- Keywords:
italic>α-conotoxin ArIB[V11L,V16D];
isulfide bond modification;
peptide-drug conjugate;
fluorescent probe
- From:
Acta Pharmaceutica Sinica
2023;58(9):2727-2733
- CountryChina
- Language:Chinese
-
Abstract:
italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.
