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Receptor mimicking TGF-beta 1 binding peptide for targeting TGF-beta 1 signaling

机译:用于瞄准TGF-β1的受体用于靶向TGF-β1信号传导的结合肽

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摘要

Prolonged and elevated transforming growth factor-beta 1 (TGF-beta 1) signaling can lead to undesired scar formation during tissue repair and fibrosis that is often a result of chronic inflammation in the lung, kidney, liver, heart, skin, and joints. We report new TGF-beta 1 binding peptides that interfere with TGF-beta 1 binding to its cognate receptors and thus attenuate its biological activity. We identified TGF-beta 1 binding peptides from the TGF-beta 1 binding domains of TGF-beta receptors and engineered their sequences to facilitate chemical conjugation to biomaterials using molecular docking simulations. The in vitro binding studies and cell-based assays showed that RIP Delta, which was derived from TGF-beta type I receptor, bound TGF-beta 1 in a sequence-specific manner and reduced the biological activity of TGF-beta 1 when the peptide was presented either in soluble form or conjugated to a commonly used synthetic biomaterial. This approach may have implications for clinical applications such as treatment of various fibrotic diseases and soft tissue repair and offer a design strategy for peptide antibodies based on the biomimicry of ligand-receptor interactions.
机译:延长和升高的转化生长因子-β1(TGF-β1)信号传导可能导致在组织修复和纤维化期间导致不希望的瘢痕形成,这通常是肺,肾,肝,心脏,皮肤和关节慢性炎症的结果。我们报告了新的TGF-β1结合肽,其干扰TGF-β1与其同源受体结合,从而减弱其生物活性。我们鉴定了来自TGF-β1的TGF-Beta 1结合结构域的TGF-β1结合肽,并使用分子对接模拟工程化其序列以促进化学缀合与生物材料。体外结合研究和基于细胞的测定表明,衍生自TGF-β型I受体的RIPδ以序列特异性方式结合TGF-β1,并在肽时降低TGF-β1的生物活性以可溶性形式呈现或与常用的合成生物材料缀合。这种方法可能对临床应用有影响,例如治疗各种纤维化疾病和软组织修复,并基于配体 - 受体相互作用的生物体提供肽抗体的设计策略。

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