Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Design and Prototyping, Department of Medical Technology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Biomolecules. 2023 Jun 5;13(6):942. doi: 10.3390/biom13060942.
The occurrence of accidental nerve damage during surgery and the increasing application of image guidance during head-and-neck surgery have highlighted the need for molecular targeted nerve-sparing interventions. The implementation of such interventions relies on the availability of nerve-specific tracers. In this paper, we describe the development of a truncated peptide that has an optimized affinity for protein zero (P0), the most abundant protein in myelin.
Further C- and N-terminal truncation was performed on the lead peptide Cy5-P0. The resulting nine Cy5-labelled peptides were characterized based on their photophysical properties, P0 affinity, and in vitro staining. These characterizations were combined with evaluation of the crystal structure of P0, which resulted in the selection of the optimized tracer Cy5-P0. A near-infrared Cy7-functionalized derivative (Cy7-P0) was used to perform an initial evaluation of fluorescence-guided surgery in a porcine model.
Methodological truncation of the 26-amino-acid lead compound Cy5-P0 resulted in a size reduction of 53.8% for the optimized peptide Cy5-P0. The peptide design and the 1.5-fold affinity gain obtained after truncation could be linked to interactions observed in the crystal structure of the extracellular portion of P0. The near-infrared analogue Cy7-P0 supported nerve illumination during fluorescence-guided surgery in the head-and-neck region in a porcine model.
Methodological truncation yielded a second-generation P0-specific peptide. Initial surgical evaluation suggests that the peptide can support molecular targeted nerve imaging.
手术过程中意外神经损伤的发生和头颈外科中图像引导应用的增加，突出了对分子靶向神经保护干预的需求。此类干预措施的实施依赖于神经特异性示踪剂的可用性。在本文中，我们描述了一种截短肽的开发，该肽对髓鞘中最丰富的蛋白零（P0）具有优化的亲和力。
对先导肽 Cy5-P0 进行进一步的 C 端和 N 端截断。对得到的 9 个 Cy5 标记肽进行基于光物理性质、P0 亲和力和体外染色的特性描述。这些特性与 P0 晶体结构的评估相结合，从而选择优化的示踪剂 Cy5-P0。使用近红外 Cy7 功能化衍生物（Cy7-P0）在猪模型中初步评估荧光引导手术。
对 26 个氨基酸的先导化合物 Cy5-P0 的方法学截断导致优化肽 Cy5-P0 的大小减少了 53.8%。肽设计和截断后获得的 1.5 倍亲和力增益可与 P0 细胞外部分晶体结构中观察到的相互作用相关联。近红外类似物 Cy7-P0 支持在猪模型头颈部荧光引导手术中进行神经照明。
方法学截断产生了第二代 P0 特异性肽。初步手术评估表明，该肽可以支持分子靶向神经成像。
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