Targeting Human Islet Amyloid Polypeptide Aggregation and Toxicity in Type 2 Diabetes: An Overview of Peptide-Based Inhibitors,Chemical Research in Toxicology

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Targeting Human Islet Amyloid Polypeptide Aggregation and Toxicity in Type 2 Diabetes: An Overview of Peptide-Based Inhibitors
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-10-30 , DOI: 10.1021/acs.chemrestox.0c00416
Rajneet Kaur Saini ₁ , Deepti Goyal ₁ , Bhupesh Goyal ₂

Affiliation

Type 2 diabetes (T2D) is a chronic metabolic disease characterized by insulin resistance and a progressive loss of pancreatic islet β-cell mass, which leads to insufficient secretion of insulin and hyperglycemia. Emerging evidence suggests that toxic oligomers and fibrils of human islet amyloid polypeptide (hIAPP) contribute to the death of β-cells and lead to T2D pathogenesis. These observations have opened new avenues for the development of islet amyloid therapies for the treatment of T2D. The peptide-based inhibitors are of great value as therapeutic agents against hIAPP aggregation in T2D owing to their biocompatibility, feasibility of synthesis and modification, high specificity, low toxicity, proteolytic stability (modified peptides), and weak immunogenicity as well as the large size of involved interfaces during self-aggregation of hIAPP. An understanding of what has been done and achieved will provide key insights into T2D pathology and assist in the discovery of more potent drug candidates for the treatment of T2D. In this article, we review various peptide-based inhibitors of hIAPP aggregation, including those derived from the hIAPP sequence and those not based on the sequence, consisting of both natural as well as unnatural amino acids and their derivatives. The present review will be beneficial in advancing the field of peptide medicine for the treatment of T2D.

中文翻译：

靶向 2 型糖尿病中人胰岛淀粉样多肽的聚集和毒性：基于肽的抑制剂概述

2 型糖尿病 (T2D) 是一种慢性代谢性疾病，其特征是胰岛素抵抗和胰岛 β 细胞团进行性丢失，导致胰岛素分泌不足和高血糖。新出现的证据表明，人胰岛淀粉样多肽 (hIAPP) 的有毒寡聚体和原纤维会导致 β 细胞死亡并导致 T2D 发病机制。这些观察结果为开发用于治疗 T2D 的胰岛淀粉样蛋白疗法开辟了新途径。基于肽的抑制剂由于其生物相容性、合成和修饰的可行性、高特异性、低毒性、蛋白水解稳定性（修饰肽）、弱免疫原性以及大尺寸等优点，作为治疗 T2D 中 hIAPP 聚集的药物具有重要价值。 hIAPP 自聚合过程中涉及的接口的数量。了解已完成和取得的成果将提供对 T2D 病理学的关键见解，并有助于发现治疗 T2D 的更有效的候选药物。在本文中，我们回顾了 hIAPP 聚集的各种基于肽的抑制剂，包括源自 hIAPP 序列的抑制剂和不基于该序列的抑制剂，包括天然和非天然氨基酸及其衍生物。本综述将有利于推进用于治疗 T2D 的肽药物领域。包括衍生自 hIAPP 序列的那些和不基于该序列的那些，由天然和非天然氨基酸及其衍生物组成。本综述将有利于推进用于治疗 T2D 的肽药物领域。包括衍生自 hIAPP 序列的那些和不基于该序列的那些，由天然和非天然氨基酸及其衍生物组成。本综述将有利于推进用于治疗 T2D 的肽药物领域。

更新日期：2020-11-16

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