Site-Specific Conjugated Insulin-like Growth Factor-I for Anabolic Therapy

Insulin-like growth factor-I (IGF-I) is an inducer of skeletal muscle hypertrophy and blocks skeletal muscle atrophy, rendering it a good therapeutic option for the treatment of severe burn injury for which localized treatment options are particularly interesting. For that, the therapeutic was redesigned via amber codon expression, leading to a propargyl-L-lysine (plk) modified IGF-I (plk-IGF-I Ea) with Ea peptide prolongation at the C-terminus, thereby becoming a substrate for copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) and other bio-orthogonal click chemistries. The plk-IGF-I Ea was site-specifically immobilized to agarose particles, resulting in homogeneous product outcome with retained potency while providing the necessary tools to maximize local and minimize systemic exposure. IGF-I decorated particles outperformed soluble IGF-I in C2C12 induced myotube formation, reflecting the impact of controlled multivalence on decorated materials.