胎盘碱性磷酸酶
化学
碱性磷酸酶
配体(生物化学)
体内
分子生物学
赫拉
荧光素
体外
磷酸酶
生物化学
酶
受体
生物
荧光
遗传学
物理
量子力学
作者
Gabriele Bassi,Nicholas Favalli,Christian Pellegrino,Yuichi Onda,Jörg Scheuermann,Samuele Cazzamalli,Markus G. Manz,Dario Neri
标识
DOI:10.1021/acs.jmedchem.1c01103
摘要
Placental alkaline phosphatase (PLAP) is an abundant surface antigen in the malignancies of the female reproductive tract. Nevertheless, the discovery of PLAP-specific small organic ligands for targeting applications has been hindered by ligand cross-reactivity with the ubiquitous tissue non-specific alkaline phosphatase (TNAP). In this study, we used DNA-encoded chemical libraries to discover a potent (IC50 = 32 nM) and selective PLAP inhibitor, with no detectable inhibition of TNAP activity. Subsequently, the PLAP ligand was conjugated to fluorescein; it specifically bound to PLAP-positive tumors in vitro and targeted cervical cancer in vivo in a mouse model of the disease. Ultimately, the fluorescent derivative of the PLAP inhibitor functioned as a bispecific engager redirecting the killing of chimeric antigen receptor-T cells specific to fluorescein on PLAP-positive tumor cells.
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