A Next-Generation Brain-Targeting Peptide: KS-487 Rivals Angiopep-2 in BBB Penetration with Enhanced Selectivity.

IF 3.9 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Pub Date : 2025-09-11 DOI:10.1021/acs.bioconjchem.5c00352

Kensuke Asukabe, Nagi Yamashita, Runa Fujimoto, Kotaro Sakamoto, Eijiro Miyako

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Abstract

KS-487 is a cyclic peptide previously reported to bind low-density lipoprotein receptor-related protein 1 (LRP1) and exhibit blood-brain barrier (BBB) permeability. In this study, we evaluated the in vivo BBB permeability and selectivity of KS-487 in comparison with those of Angiopep-2 (ANG2), a widely used linear LRP1-binding peptide. Indocyanine green (ICG)-labeled KS-487 and ANG2 were subcutaneously administered to mice, and their biodistribution was assessed at 24, 48, and 72 h by using in vivo imaging. ICG-KS-487 and ICG-ANG2 displayed comparable brain permeability and nearly identical time-course profiles. Notably, ICG-KS-487 demonstrated greater brain selectivity, defined as the ratio of brain to liver accumulation at 72 h. No adverse effects, including weight loss or histopathological abnormalities in major organs, were observed in mice treated with ICG-KS-487. These findings highlight the remarkable brain-targeting properties and safety profile of KS-487, supporting its potential utility as a targeting ligand for drug delivery to treat brain-related disorders.

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新一代脑靶向肽：KS-487与Angiopep-2在血脑屏障穿透中的选择性增强

KS-487是一种环肽，先前报道与低密度脂蛋白受体相关蛋白1 （LRP1）结合，并表现出血脑屏障（BBB）渗透性。在这项研究中，我们比较了KS-487与Angiopep-2（一种广泛使用的线性lrp1结合肽）的体内血脑屏障通透性和选择性。将吲哚菁绿（ICG）标记的KS-487和ANG2皮下给予小鼠，并在24、48和72 h通过体内成像评估其生物分布。ICG-KS-487和ICG-ANG2显示相当的脑通透性和几乎相同的时间过程谱。值得注意的是，ICG-KS-487表现出更大的脑选择性，定义为72h时脑与肝脏积累的比率。在使用ICG-KS-487治疗的小鼠中，没有观察到包括体重减轻或主要器官组织病理异常在内的不良反应。这些发现突出了KS-487显著的脑靶向特性和安全性，支持其作为靶向配体治疗脑相关疾病的潜在用途。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioconjugate Chemistry 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.