Huarui Zhang, Sifan Yu, Shuaijian Ni, Amu Gubu, Yuan Ma, Yihao Zhang, Haitian Li, Yuzhe Wang, Luyao Wang, Zongkang Zhang, Yuanyuan Yu, Aiping Lyu, Baoting Zhang, Ge Zhang
The molecular weight of nucleic acid aptamers (20 kDa) is lower than the cutoff threshold of the renal filtration (30-50 kDa), resulting in a very short half-life, which dramatically limits their druggability. To address this, we utilized 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(4-hydroxy-2-oxo-2H-chromen-6-yl)propenamide (HC) and 12-((2,5-dioxopyrrolidin-1-yl)oxy)-12-oxododecanoic acid (DA), two newly designed coupling agents, for synergistic binding to human serum albumin (HSA). Both HC and DA are conjugated to a bone anabolic aptamer (Apc001) against sclerostin to form an Apc001OC conjugate with high binding affinity to HSA...
December 12, 2023: Molecular Therapy. Nucleic Acids