“Site-specific Albumination for the Prolonged Serum Half-life of Therapeutic Proteins”
Therapeutic proteins have been widely used to treat various human diseases. However, short half-lives of proteins in vivo have often limited developing new proteins and expending applications of existing therapeutic proteins. Conjugation of poly ethyleneglycol (PEG) was a conventional strategy to prolong half-life of therapeutic proteins in vivo. However, PEG conjugation raised several concerns, such as accumulation in vivo and immunogenicity. As an emerging half-life extender alternative to PEG, human serum albumin (HSA) received a great attention thanks to its exceptionally long half-life (over three weeks). We achieved the site-specific conjugation of HSA to therapeutic protein using strain-promoted azide alkyne cycloaddition (SPAAC) and site-specific incorporation of p-azidophenylalanine, resulting in the substantially prolonged serum half-life in vivo. Fatty acids are natural albumin ligands. Albumin binding domains are short peptides with a high affinity to albumin. We also demonstrated the site-specific conjugation of fatty acid/albumin binding domain to proteins via click chemistries effectively prolonged serum half-life in vivo.
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