Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA.
Calico Life Sciences, 1170 Veterans Boulevard, 94080, South San Francisco, CA, USA.
Angew Chem Int Ed Engl. 2023 May 2;62(19):e202300289. doi: 10.1002/anie.202300289. Epub 2023 Apr 3.
α-Klotho, an aging-related protein found in the kidney, parathyroid gland, and choroid plexus, acts as an essential co-receptor with the fibroblast growth factor 23 receptor complex to regulate serum phosphate and vitamin D levels. Decreased levels of α-Klotho are a hallmark of age-associated diseases. Detecting or labeling α-Klotho in biological milieu has long been a challenge, however, hampering the understanding of its role. Here, we developed branched peptides by single-shot parallel automated fast-flow synthesis that recognize α-Klotho with improved affinity relative to their monomeric versions. These peptides were further shown to selectively label Klotho for live imaging in kidney cells. Our results demonstrate that automated flow technology enables rapid synthesis of complex peptide architectures, showing promise for future detection of α-Klotho in physiological settings.
α-Klotho 是一种与衰老相关的蛋白，存在于肾脏、甲状旁腺和脉络丛中，作为成纤维细胞生长因子 23 受体复合物的必需共受体，调节血清磷酸盐和维生素 D 水平。α-Klotho 水平降低是与年龄相关疾病的标志。然而，在生物环境中检测或标记 α-Klotho 一直是一个挑战，阻碍了对其作用的理解。在这里，我们通过单次并行自动化快速流动合成技术开发了支化肽，与单体形式相比，这些支化肽识别 α-Klotho 的亲和力得到了提高。这些肽还被进一步证明可以选择性标记肾脏细胞中的 Klotho 进行活细胞成像。我们的结果表明，自动化流动技术能够快速合成复杂的肽结构，为未来在生理环境中检测 α-Klotho 提供了希望。
