转谷氨酰胺酶催化的共价作用。

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2024-08-26 DOI:10.1016/j.ejpb.2024.114462
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引用次数: 0

摘要

大自然通过催化与组织细胞外基质(ECM)的共价键来实现蛋白质和肽的储存。我们正在将这一自然蓝图转化为肌节蛋白抑制肽(Anti-Myo)的持续递送,从而通过注射溶液建立酶库。为此,我们将 Anti-Myo 与转谷氨酰胺酶(TG)底物胰岛素样生长因子 I 的 D 域融合。在生物工程 ECM 和小鼠体内,TG 可催化 D 域与层粘连蛋白和纤连蛋白等 ECM 蛋白的共价结合。用 Anti-Myo 装饰的 ECM 可抑制肌生成蛋白的活性和通路激活,并减少体外预处理的骨髓巨噬细胞向破骨细胞的分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Transglutaminase-catalyzed covalent

Nature realizes protein and peptide depots by catalyzing covalent bonds with the extracellular matrix (ECM) of tissues. We are translating this natural blueprint for the sustained delivery of a myostatin-inhibiting peptide (Anti-Myo), resulting in an enzyme depot established from injectable solutions. For that, we fused Anti-Myo to the D-domain of insulin-like growth factor I, a transglutaminase (TG) substrate. TG catalyzed the covalent binding of the D-domain to ECM proteins, such as laminin and fibronectin, on bioengineered ECM and in mice. ECM decorated with Anti-Myo suppressed myostatin activity and pathway activation and reduced the differentiation of preconditioned bone marrow-derived macrophages into osteoclasts in vitro.

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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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