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通过在B29 Lysine B29处的 fenylalanine 结合,合成一种高度耐热的胰岛素

Shantanu Sen¹, Rafat Ali¹, Akanksha Onkar^2,3

¹Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, 208016, UP, India.

Communications chemistry

|July 23, 2024

概括

氨酸结合胰岛素 (FHI) 提供了对热和压力的增强稳定性,比原生胰岛素更长的时间抵抗动. 这一突破改善了胰岛素的性能.

科学领域:

生物化学生物化学
材料科学材料科学材料科学
内分泌学在内分泌学.

背景情况:

全球数以百万计的糖尿病患者依赖每天注射胰岛素.
胰岛素对热的敏感性和纤维化的倾向带来了大量的储存和管理挑战,特别是在缺乏可靠制冷的地区.
目前的胰岛素配方需要严格的温度控制,限制了可访问性.

研究的目的:

合成和评估具有更好的热和结构稳定性的新型人体胰岛素类似物.
研究化学结合的潜力,以增强胰岛素对热引起的降解和纤维化的抵抗.
确定有助于改性胰岛素类似物增强稳定性的特定分子相互作用.

主要方法:

通过将B29 lysine残留与酸,酸,氨酸和氨酸结合,合成四种人体胰岛素类似物.
在各种压力条件下评估胰岛素模拟的稳定性:高温 (65°C),高盐度 (25mM NaCl) 和广泛的pH范围 (1.67.4).
使用体外,体外和体内模型评估纤维化抵抗和生物活性.

主要成果:

与原生胰岛素相比,氨酸结合胰岛素 (FHI) 在热,盐和pH压力下表现出优越的稳定性.
在不同实验模型中,FHI表现出显著延长的纤维化耐药性,同时保持生物活性.
结构分析揭示了FHI中的额外的芳香 π-π 相互作用和键,在原生胰岛素中缺席,有助于其增强的稳定性.

结论:

氨结合赋予人类胰岛素显著的热和结构稳定性,创造了一个有前途的模拟物 (FHI).
FHI克服了原生胰岛素热可变性和纤维化的局限性.
这种稳定胰岛素模拟剂为改善胰岛素治疗的可访问性和疗效提供了潜在的解决方案,特别是在资源有限的环境中.

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