申请人:Lee Chyi
公开号:US20090285780A1
公开(公告)日:2009-11-19
PEG linker compounds and biologically active conjugates thereof having mixed functional group linkages attached to at least one PEG moeity, and a coupling group for attaching a biologically active molecule. The PEG mixed linkages can be the combinations of stable, or labile, or releasable, or stable and labile, or stable and releasable, or releasable and labile covalent linkages. The mixed functional linkages of the PEG linker compounds consist of different organic functional groups, which have non-equivalent half-life in plasma and, hence, they have different release rates in blood. The present invention also provides for attachment of novel PEG linker compounds with mixed functional linkages for Pegylation of biologically active molecules to produce Probiomolecule-PEG constructs. The Probiomolecule-PEG construct is the prodrug of biomolecule-PEG conjugate or biomolecule. The Probiomolecule-PEG conjugate will gradually lose portions (or all) of its PEG polymers in vivo to convert into smaller size biomolecule-PEG conjugate (or biologically active molecule), thereby increasing their biological activity in vivo.
PEG连接剂化合物及其生物活性共轭物,其混合功能基连接至少一个PEG分子,并具有用于连接生物活性分子的偶联基。PEG混合连接可以是稳定的、不稳定的、可释放的、稳定和不稳定的、稳定和可释放的、可释放和不稳定的共价连接的组合。PEG连接剂的混合功能连接由不同的有机功能基组成,在血浆中具有不同的半衰期,因此在血液中具有不同的释放速率。本发明还提供了将新型PEG连接剂与混合功能连接用于PEG化生物活性分子,以产生Probiomolecule-PEG构建物的附着。Probiomolecule-PEG构建物是生物分子-PEG共轭物或生物分子的前药。Probiomolecule-PEG共轭物将逐渐失去其体内的PEG聚合物部分(或全部),转化为更小的生物分子-PEG共轭物(或生物活性分子),从而增加它们在体内的生物活性。