The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension
Autor: | Inchan Kwon, Mi Sun Jin, Junyong Park, Jinhwan Cho, Giyoong Tae |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Serum albumin Medicine (miscellaneous) 02 engineering and technology Conjugated system Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Neonatal Fc receptor Binding site lcsh:QH301-705.5 fatty acid conjugation chemistry.chemical_classification biology Albumin Serum half-life extension Fatty acid 021001 nanoscience & nanotechnology 030104 developmental biology lcsh:Biology (General) Biochemistry chemistry FcRn-mediated recycling biology.protein 0210 nano-technology Linker Conjugate |
Zdroj: | Biomedicines Volume 8 Issue 5 Biomedicines, Vol 8, Iss 96, p 96 (2020) |
ISSN: | 2227-9059 |
Popis: | Conjugation of serum albumin or one of its ligands (such as fatty acid) has been an effective strategy to prolong the serum half-lives of drugs via neonatal Fc receptor (FcRn)&ndash mediated recycling of albumin. So far, fatty acid (FA) has been effective in prolonging the serum half-lives for therapeutic peptides and small proteins, but not for large therapeutic proteins. Very recently, it was reported a large protein conjugated to FA competes with the binding of FcRn with serum albumin, leading to limited serum half-life extension, because primary FA binding sites in serum albumin partially overlap with FcRn binding sites. In order to prevent such competition, longer linkers between FA and the large proteins were required. Herein, we hypothesized that small proteins do not cause substantial competition for FcRn binding to albumin, resulting in the extended serum half-life. Using a small protein (28 kDa), we investigated whether the intramolecular distance in FA-protein conjugate affects the FcRn binding with albumin and serum half-life using linkers with varying lengths. Unlike with the FA-conjugated large protein, all FA-conjugated small proteins with different linkers exhibited comparable the FcRn binding to albumin and extended serum half-life. |
Databáze: | OpenAIRE |
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