Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to 18F-Glycopeptides as Effective Imaging Probes for Positron Emission Tomography
Labeling and Glycosylation of Peptides Using Click Chemistry: A General Approach to 18F-Glycopeptides as Effective Imaging Probes for Positron Emission Tomography
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DOI：
10.1002/anie.200904137
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Prante, Olaf
中科院分区：
文献类型：
--
作者：
Maschauer, Simone;Einsiedel, Juergen;Prante, Olaf
在分子成像领域，正电子发射断层扫描（PET）已成为一种具有出色灵敏度的体内研究成像模式。[1]PET标记是具有挑战性的，因为短寿命的正电子发射同位素，如18F和11 C被用作标记剂。[2]快速可靠的标记策略的优化和有效应用是获得用于研究和临床试验的新放射性药物的先决条件。在体内特异性针对分子靶点的生物活性肽代表了一类重要的PET示踪剂，以促进预测性成像和PET引导的治疗。使用18F标记的辅基合成基于肽的放射性药物的多种策略已经被阐述，包括化学选择性肟缀合[3]和使用18F标记的马来酰亚胺衍生物作为半胱氨酸反应性试剂。[4，5]遵循Sharpless等人引入的点击化学的概念，[6]Huisgen [3+ 2]叠氮化物-炔环加成反应已经适用于18F-放射合成方法，以利用其在温和的CuI促进的水溶液反应条件下的选择性、可靠性和速度。[7]肽显像剂的多功能性经常受到其体内不稳定性的阻碍，因为内源性肽酶会快速降解。例如，神经降压素受体-I（NTR-1）的放射性标记的基于肽的成像剂的合成需要修饰以改善代谢稳定性，所述神经降压素受体-I（NTR-1）在许多人类癌症中过表达。[八]《中国日报》
In the field of molecular imaging, positron emission tomography (PET) has emerged as an imaging modality with excellent sensitivity for in vivo studies.[1] PET labeling is challenging since short-lived positron-emitting isotopes such as 18F and 11C are used as labeling agents.[2] The optimization and efficient application of rapid and reliable labeling strategies are prerequisites for obtaining access to new radiopharmaceuticals for both research and clinical trials. Bioactive peptides that specifically address molecular targets in vivo represent an important class of PET tracers to facilitate predictive imaging and PET-guided therapy. Diverse strategies for the synthesis of peptide-based radiopharmaceuticals using 18F-labeled prosthetic groups have been elaborated, including chemoselective oxime conjugation [3] and the use of 18F-labeled maleimide derivatives as cysteinereactive reagents.[4, 5] Following the concept of click chemistry introduced by Sharpless et al.,[6] the Huisgen [3+ 2] azide–alkyne cycloaddition has been adapted to 18F-radiosynthetic methods in order to take advantage of its selectivity, reliability, and speed under aqueous mild CuI-promoted reaction conditions.[7]The versatility of peptide imaging agents is frequently hampered by their instability in vivo because of rapid degradation by endogenous peptidases. As an example, the synthesis of radiolabeled peptide-based imaging agents for the neurotensin receptor-1 (NTR-1), which is overexpressed in a number of human cancers, requires modifications to improve the metabolic stability.[8]