Lei Jun, Sun Lichun, Huang Siyu, Zhu Chenhong, Li Ping, He Jun, Mackey Vienna, Coy David H, He Quanyong
The Third Xiangya HospitaI of Central South University Changsha, Hunan, China.
Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-pharm Co., Ltd. Shenzhen, Guangdong, China.
Am J Transl Res. 2019 Jul 15;11(7):3919-3931. eCollection 2019.
Nowadays, the bacterial drug resistance leads to serious healthy problem worldwide due to the long-term use and the abuse of traditional antibiotics result in drug resistance of bacteria. Finding a new antibiotic is becoming more and more difficult. Antimicrobial peptides (AMPs) are the host defense peptides with most of them being the cationic (positively charged) and amphiphilic (hydrophilic and hydrophobic) α-helical peptide molecules. The membrane permeability is mostly recognized as the well-accepted mechanism to describe the action of cationic AMPs. These cationic AMPs can bind and interact with the negatively charged bacterial cell membranes, leading to the change of the electrochemical potential on bacterial cell membranes, inducing cell membrane damage and the permeation of larger molecules such as proteins, destroying cell morphology and membranes and eventually resulting in cell death. These AMPs have been demonstrated to have their own advantages over the traditional antibiotics with a broad-spectrum of antimicrobial activities including anti-bacteria, anti-fungi, anti-viruses, and anti-cancers, and even overcome bacterial drug-resistance. The natural AMPs exist in a variety of organisms and are not stable with a short half-life, more or less toxic side effects, and particularly may have severe hemolytic activity. To open the clinical applications, it is necessary and important to develop the synthetic and long-lasting AMP analogs that overcome the disadvantages of their natural peptides and the potential problems for the drug candidates.
如今,由于传统抗生素的长期使用和滥用导致细菌耐药性,细菌耐药性在全球范围内引发了严重的健康问题。寻找新型抗生素变得越来越困难。抗菌肽(AMPs)是宿主防御肽,其中大多数是阳离子(带正电荷)且两亲性(亲水和疏水)的α-螺旋肽分子。膜通透性大多被认为是描述阳离子抗菌肽作用的公认机制。这些阳离子抗菌肽可以与带负电荷的细菌细胞膜结合并相互作用,导致细菌细胞膜上的电化学电位发生变化,诱导细胞膜损伤以及蛋白质等大分子的渗透,破坏细胞形态和膜结构,最终导致细胞死亡。已证明这些抗菌肽相对于传统抗生素具有自身优势,具有包括抗菌、抗真菌、抗病毒和抗癌在内的广谱抗菌活性,甚至能克服细菌耐药性。天然抗菌肽存在于多种生物体中,不稳定,半衰期短,或多或少有毒副作用,尤其可能具有严重的溶血活性。为了开启临床应用,开发克服天然肽缺点以及候选药物潜在问题的合成且长效的抗菌肽类似物是必要且重要的。