Site-Specific Conjugated Insulin-like Growth Factor-I for Anabolic Therapy,ACS Biomaterials Science & Engineering

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Site-Specific Conjugated Insulin-like Growth Factor-I for Anabolic Therapy
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-02-12 00:00:00 , DOI: 10.1021/acsbiomaterials.7b01016
Fang Wu ₁ , Alexandra Braun ₁ , Tessa Lühmann ₁ , Lorenz Meinel ₁

Affiliation

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.

中文翻译：

定点特异性共轭胰岛素样生长因子-I的同化疗法。

胰岛素样生长因子-I（IGF-I）是骨骼肌肥大的诱导剂，可阻断骨骼肌萎缩，使其成为治疗严重烧伤的良好治疗选择，对于局部烧伤尤为关注。为此，治疗经由琥珀密码子表达重新设计，导致炔丙基升-赖氨酸（plk）修饰的IGF-I（plk-IGF-I Ea）在C端具有Ea肽延长，从而成为铜（I）催化的叠氮化物炔烃环加成（CuAAC）和其他生物正交点击的底物化学。将plk-IGF-I Ea特异性地固定在琼脂糖颗粒上，从而产生均一的产品结果，并保留了效力，同时提供了必要的工具来最大化局部和最小化全身暴露。在C2C12诱导的肌管形成过程中，IGF-I装饰颗粒的性能优于可溶性IGF-I，这反映了受控多价对装饰材料的影响。

更新日期：2018-02-12

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