The Minimal Effect of Linker Length for Fatty Acid Conjugation to a Small Protein on the Serum Half-Life Extension.

摘要: Conjugation of serum albumin or one its ligands (such as fatty acid) has been an effective strategy to prolong the half-lives drugs via neonatal Fc receptor (FcRn)–mediated recycling albumin. So far, acid (FA) in prolonging for therapeutic peptides and small proteins, but not large proteins. Very recently, it was reported a protein conjugated FA competes with binding FcRn albumin, leading limited half-life extension, because primary sites partially overlap sites. In order prevent such competition, longer linkers between proteins were required. Herein, we hypothesized that do cause substantial competition resulting extended half-life. Using (28 kDa), investigated whether intramolecular distance FA-protein conjugate affects using varying lengths. Unlike FA-conjugated protein, all different exhibited comparable