Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.

Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.
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亲和成像质谱 (AIMS):高通量筛选特定小分子与冷冻组织切片的相互作用。

DOI:
10.1039/c5an01381j
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发表时间:
2015
期刊:
影响因子:
4.2
通讯作者:
Takikawa O.
Takikawa O.
中科院分区:
化学2区
文献类型:
--
作者:
Yoshimi T;Kawabata S;Taira S;Okuno A;Mikawa R;Murayama S;Tanaka K;Takikawa O.

文献摘要

相似文献

一种使用亲和成像质谱 (AIMS) 的新型筛选系统已被开发出来,用于识别未固定人体组织中的蛋白质聚集体或器官结构。将冷冻组织切片放置在小型(毫米级)不锈钢芯片上,并与大量小分子库一起孵育。通过成像质谱 (IMS) 鉴定对组织切片具有特异性亲和力的候选分子。作为一个示例应用,我们筛选了 1000 多种针对阿尔茨海默氏病 (AD) 脑组织的化合物,并鉴定了与年龄匹配的对照相比,对含有 tau 沉积物的 AD 脑切片具有高亲和力的几种化合物。还应该可以使用 AIMS 来分离对因氧化、磷酸化、乙酰化、聚集、外消旋或截短等事件(例如由于老化)而广泛改变的组织结构或成分具有亲和力的化合物。它也可能适用于生物标志物筛选计划。
A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs.