公开(公告)号：US09642922B2

公开(公告)日：2017-05-09

申请号：US14464111

申请日：2014-08-20

申请人： The Board of Trustees of the Leland Stanford Junior University

发明人： Jianghong Rao ,  Deju Ye ,  Adam Shuhendler ,  Frederick Te-Ning Chin ,  Jongho Jeon ,  Bin Shen

IPC分类号： A61K51/00 ,  A61M36/14 ,  A61K49/00 ,  A61K49/08 ,  G01N33/50 ,  A61K49/10 ,  A61K51/04

CPC分类号： A61K49/0002 ,  A61K49/0021 ,  A61K49/0032 ,  A61K49/0041 ,  A61K49/0052 ,  A61K49/085 ,  A61K49/101 ,  A61K51/0455 ,  G01N33/5005 ,  G01N2333/96469 ,  G01N2510/00

摘要： Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

公开(公告)号：US20150056137A1

公开(公告)日：2015-02-26

申请号：US14464111

申请日：2014-08-20

申请人： The Board of Trustees of the Leland Stanford Junior University

发明人： Jianghong Rao ,  Deju Ye ,  Adam Shuhendler ,  Frederick Te-Ning Chin ,  Jongho Jeon ,  Bin Shen

IPC分类号： A61K51/08 ,  A61K49/08 ,  G01N33/52 ,  A61K49/00

CPC分类号： A61K49/0002 ,  A61K49/0021 ,  A61K49/0032 ,  A61K49/0041 ,  A61K49/0052 ,  A61K49/085 ,  A61K49/101 ,  A61K51/0455 ,  G01N33/5005 ,  G01N2333/96469 ,  G01N2510/00

摘要： Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

摘要翻译： 提供了一种可激活的探针，其在肽酶引发，最有利的是胱天蛋白酶-3激活时，经历分子内环化和随后在凋亡性肿瘤细胞中的聚集。 这些胱天蛋白酶敏感的纳米聚集探针（C-SNAF）通常是生物相容性的，具有NIR光谱性质或可以用作PET或MRI成像剂，并且具有适于体内使用的靶向介导的纳米结构自组装的机制。 探针包括与氨基荧光素支架连接的D-半胱氨酸和2-氰基-6-羟基喹啉（CHQ）部分的生物相容性缩合化学产物，其可以通过需要半胱天冬酶-3 / 7- 介导的天冬氨酸 - 谷氨酸 - 缬氨酸 - 天冬氨酸（L-DEVD）封端肽的切割和游离的细胞内硫醇介导的二硫键的还原。