Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu 730000, China.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, Gansu 730000, China.
J Med Chem. 2023 May 25;66(10):6617-6630. doi: 10.1021/acs.jmedchem.2c02021. Epub 2023 Mar 9.
Wound healing is a complex process that can be delayed in some pathological conditions, such as infection and diabetes. Following skin injury, the neuropeptide substance P (SP) is released from peripheral neurons to promote wound healing by multiple mechanisms. Human hemokinin-1 (hHK-1) has been identified as an SP-like tachykinin peptide. Surprisingly, hHK-1 shares similar structural features with antimicrobial peptides (AMPs), but it does not display efficient antimicrobial activity. Therefore, a series of hHK-1 analogues were designed and synthesized. Among these analogues, AH-4 was found to display the greatest antimicrobial activity against a broad spectrum of bacteria. Furthermore, AH-4 rapidly killed bacteria by membrane disruption, similar to most AMPs. More importantly, AH-4 showed favorable healing activity in all tested mouse full-thickness excisional wound models. Overall, this study suggests that the neuropeptide hHK-1 can be used as a desirable template for developing promising therapeutics with multiple functions for wound healing.
伤口愈合是一个复杂的过程，在某些病理条件下可能会延迟，例如感染和糖尿病。在皮肤损伤后，神经肽物质 P（SP）从周围神经元释放出来，通过多种机制促进伤口愈合。人类血激肽-1（hHK-1）已被确定为一种类似 SP 的速激肽肽。令人惊讶的是，hHK-1 与抗菌肽（AMPs）具有相似的结构特征，但它没有显示出有效的抗菌活性。因此，设计并合成了一系列 hHK-1 类似物。在这些类似物中，发现 AH-4 对广谱细菌表现出最大的抗菌活性。此外，AH-4 通过破坏细胞膜迅速杀死细菌，类似于大多数 AMPs。更重要的是，AH-4 在所有测试的小鼠全层切口伤口模型中均显示出良好的愈合活性。总的来说，这项研究表明，神经肽 hHK-1 可用作开发具有多种伤口愈合功能的有前途治疗剂的理想模板。
