Crystal structure of human serum albumin in complex with megabody reveals unique human and murine cross-reactive binding site.

ABSTRACT: The pharmacokinetic properties of small biotherapeutics can be enhanced via conjugation to cross-reactive albumin-binding ligands in a process that improves their safety and accelerates testing through multiple pre-clinical animal models. In this context, the small and stable heavy-chain-only nanobody NbAlb1, capable of binding both human and murine albumin, has recently been successfully applied to improve the stability and prolong the in vivo plasma residence time of multiple small therapeutic candidates. Despite its clinical efficacy, the mechanism of cross-reactivity of NbAlb1 between human and murine serum albumins has not yet been investigated. To unveil the molecular basis of such an interaction, we solved the crystal structure of human serum albumin (hSA) in complex with NbAlb1. Th

SUBMITTER: De Felice S 

PROVIDER: S-EPMC10804666 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature