Branched Multimeric Peptides as Affinity Reagents for the Detection of α-Klotho Protein.

Autor:	Ye X; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA., Zhang P; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA., Wang JCK; Calico Life Sciences, 1170 Veterans Boulevard, 94080, South San Francisco, CA, USA., Smith CL; AbbVie Bioresearch Center, 100 Research Drive, 01605, Worcester, MA, USA., Sousa S; AbbVie Bioresearch Center, 100 Research Drive, 01605, Worcester, MA, USA., Loas A; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA., Eaton DL; Calico Life Sciences, 1170 Veterans Boulevard, 94080, South San Francisco, CA, USA., Preciado López M; Calico Life Sciences, 1170 Veterans Boulevard, 94080, South San Francisco, CA, USA., Pentelute BL; Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, 02142, MA, USA.; Center for Environmental Health Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 02139, Cambridge, MA, USA.; Broad Institute of MIT and Harvard, 415 Main Street, 02142, Cambridge, MA, USA.
Jazyk:	angličtina
Zdroj:	Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 May 02; Vol. 62 (19), pp. e202300289. Date of Electronic Publication: 2023 Apr 03.
DOI:	10.1002/anie.202300289
Abstrakt:	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. (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze:	MEDLINE
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