The human CD98 heavy chain (CD98hc) offers a promising biomedical target both for tumor therapy and for drug delivery to the brain. We have previously developed a cognate Anticalin protein with picomolar affinity and demonstrated its effectiveness in a xenograft animal model. Due to the lack of cross‐reactivity with the murine ortholog, we now report the development and X‐ray structural analysis of an Anticalin with high affinity toward CD98hc from mouse. This binding protein recognizes the same protruding epitope loop—despite distinct structure—in the membrane receptor ectodomain as the Anticalin selected against human CD98hc. Thus, this surrogate Anticalin should be useful for the preclinical assessment of CD98hc targeting in vivo and support the translational development for medical application in humans.

中文翻译：

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针对小鼠CD98hc的临床前研究的替代Anticalin蛋白的设计。

人CD98重链（CD98hc）为肿瘤治疗和向大脑的药物输送提供了有希望的生物医学靶标。我们先前已经开发出了具有皮摩尔亲和力的同源Anticalin蛋白，并证明了其在异种移植动物模型中的有效性。由于缺乏与鼠直系同源物的交叉反应性，我们现在报道对小鼠抗CD98hc具有高度亲和力的Anticalin的开发和X射线结构分析。该结合蛋白在膜受体胞外域中识别出与针对人CD98hc所选择的Anticalin相同的突出表位环（尽管结构不同）。因此，这种替代品Anticalin对体内靶向CD98hc的临床前评估应是有用的，并支持在人类医学应用中的翻译开发。