Hybrid fusion protein as a dual protease inhibitor for the healing of chronic wounds.

Hybrid fusion protein as a dual protease inhibitor for the healing of chronic wounds.
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DOI:
10.1002/btpr.3209
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发表时间:
2021-11
影响因子:
2.9
通讯作者:
Koria P
Koria P
中科院分区:
工程技术4区
文献类型:
--
作者:
Strauss G;Koria P

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疾病需要针对疾病的各个具体方面进行干预。通常,复杂疾病的缓解是通过将治疗、药物和治疗方法混合在一起来实现的,其中它们可能彼此产生负面相互作用,或者永远不会作为全身异质混合物到达患病部位。慢性伤口非常复杂,因为它们非常局部化并且有自己的环境,其中由于高水平的多种蛋白酶导致的组织解构超过了正常组织的重建。这一想法导致需要一种蛋白质,其具有用于局部治疗的低扩散率、对抗导致短链肽降解的高浓度蛋白水解物质的强度,同时对多种蛋白酶具有广泛的抑制作用。类弹性蛋白肽是一种有吸引力的、热响应性的、基于蛋白质的药物递送伙伴,因为它们具有低扩散性,并且可作为短链肽融合的稳定结构。在该项目中,创建了一种新型弹性蛋白样肽蛋白,以抑制人中性粒细胞弹性蛋白酶和基质金属蛋白酶-2。作为一种生物制品,它是独一无二的,因为它是一种针对多种蛋白酶具有特定生物活性的蛋白质,最终显示出在一个氨基酸序列内混合和匹配不同生物活性肽的潜力。
Diseases bring about the need for interventions that pinpoint each specific aspect of the illness. Commonly, remission of a complex disease is accomplished by mixing treatments, medications, and therapeutics together in a fashion where they may negatively interact with each other or never arrive at the diseased site as a systemic heterogeneous mixture. Chronic wounds display intricacy as they are very localized and have their own environment where tissue deconstruction due to high levels of numerous proteases outweighs normal tissue reconstruction. This idea leads to the necessity of a protein that contains low diffusivity rates for localized treatment, strength against high concentrations of proteolytic species that lead to degradation of short chain peptides, while encompassing broad inhibitory effects against multiple proteases. Elastin-Like Peptides are an attractive, thermoresponsive, protein-based drug delivery partner as they contain low diffusivity and serve as a stable architecture for short chain peptide fusion. In this project, a novel elastin-like peptide-based protein has been created to target the inhibition of both human neutrophil elastase and matrix metalloprotease-2. As a biologic, this is unique as it is a protein with specific biological activities against multiple proteases, ultimately displaying the potential to mix and match differing biologically active peptides within one amino acid sequence.
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