甲基乙二醛诱导修饰稳定治疗蛋白:综述。

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nainika Prashant Kotian, Anusha Prabhu, Tenzin Tender, Hariharapura Raghu Chandrashekar
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引用次数: 0

摘要

治疗性蛋白质是一种有效的速效药物,对治疗各种疾病都非常有效。药用蛋白的使用在过去十年中有所增加,随着我们更好地了解疾病的分子途径,它将进一步发展。然而,它的加工成本高,稳定性有限,难以作为口服药物使用,以及大蛋白无法穿透组织并到达目标位置。已经开发了许多方法来克服治疗蛋白的稳定性和伴侣活性问题,即添加外部剂(通过使用稳定赋形剂改变周围溶剂的性质,例如氨基酸、糖、多元醇)和内部剂(影响其结构性质的化学修饰,例如突变、糖基化)。然而,这些方法必须完全清除蛋白质不稳定性和伴侣问题。在微调伴侣蛋白以提高其生物功效和稳定性方面仍有许多工作要做。甲基乙二醛(MGO)是一种有效的二羰基化合物,与蛋白质反应并形成共价交联。由于已知MGO清除剂会改变蛋白质结构,从而可能导致生物活性和稳定性的改变,因此对MGO清除剂进行了大量研究。MGO在我们体内自然产生,然而,它对伴侣和蛋白质稳定性的影响需要更好地理解,并且似乎根据浓度而变化。本文综述了几个研究小组在MGO对各种蛋白质的影响方面所做的努力。它还研究了MGO对客户蛋白α-晶体蛋白的影响,以了解蛋白质伴侣和稳定性问题的潜在解决方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Methylglyoxal Induced Modifications to Stabilize Therapeutic Proteins: A Review

Methylglyoxal Induced Modifications to Stabilize Therapeutic Proteins: A Review

Therapeutic proteins are potent, fast-acting drugs that are highly effective in treating various conditions. Medicinal protein usage has increased in the past 10 years, and it will evolve further as we better understand disease molecular pathways. However, it is associated with high processing costs, limited stability, difficulty in being administered as an oral medication, and the inability of large proteins to penetrate tissue and reach their target locations. Many methods have been developed to overcome the problems with the stability and chaperone activity of therapeutic proteins, viz., the addition of external agents (changing the properties of the surrounding solvent by using stabilizing excipients, e.g., amino acids, sugars, polyols) and internal agents (chemical modifications that influence its structural properties, e.g., mutations, glycosylation). However, these methods must completely clear protein instability and chaperone issues. There is still much work to be done on finetuning chaperone proteins to increase their biological efficacy and stability. Methylglyoxal (MGO), a potent dicarbonyl compound, reacts with proteins and forms covalent cross-links. Much research on MGO scavengers has been conducted since they are known to alter protein structure, which may result in alterations in biological activity and stability. MGO is naturally produced within our body, however, its impact on chaperones and protein stability needs to be better understood and seems to vary based on concentration. This review highlights the efforts of several research groups on the effect of MGO on various proteins. It also addresses the impact of MGO on a client protein, α-crystallin, to understand the potential solutions to the protein’s chaperone and stability problems.

Graphical Abstract

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来源期刊
The Protein Journal
The Protein Journal 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
57
审稿时长
12 months
期刊介绍: The Protein Journal (formerly the Journal of Protein Chemistry) publishes original research work on all aspects of proteins and peptides. These include studies concerned with covalent or three-dimensional structure determination (X-ray, NMR, cryoEM, EPR/ESR, optical methods, etc.), computational aspects of protein structure and function, protein folding and misfolding, assembly, genetics, evolution, proteomics, molecular biology, protein engineering, protein nanotechnology, protein purification and analysis and peptide synthesis, as well as the elucidation and interpretation of the molecular bases of biological activities of proteins and peptides. We accept original research papers, reviews, mini-reviews, hypotheses, opinion papers, and letters to the editor.
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