Strategic modification of low-activity natural antimicrobial peptides confers antibacterial potential in vitro and in vivo

被引：20

作者：

Hazam, Prakash Kishore ^{[1
]}

Cheng, Chih-Cheng ^{[2
]}

Lin, Wen-Chun ^{[1
]}

Hsieh, Chu-Yi ^{[1
]}

Hsu, Po-Hsien ^{[2
,7
,8
]}

Chen, Yun-Ru ^{[3
]}

Li, Chao -Chin ^{[4
]}

Hsueh, Po-Ren ^{[5
,6
,9
]}

Chen, Jyh-Yih ^{[1
,10
,11
,12
,13
]}

机构：

[1] Acad Sinica, Inst Cellular & Organism Biol, Marine Res Stn, 23-10 Dahuen Rd, Ilan 262, Taiwan

[2] Natl Taiwan Univ, Inst Fisheries Sci, 1 Roosevelt Rd,Sec 4, Taipei 106, Taiwan

[3] Acad Sinica, Inst Biol Chem, Acad Sinica Prot Clin, 128 Acad Rd,Sect 2, Taipei 115, Taiwan

[4] Acad Sinica, Inst Cellular & Organism Biol, Taipei 115, Taiwan

[5] China Med Univ, China Med Univ Hosp, Sch Med, Dept Lab Med, Taichung, Taiwan

[6] China Med Univ, China Med Univ Hosp, Sch Med, Dept Internal Med, Taichung, Taiwan

[7] China Med Univ, Sch Med, PhD Program Aging, Taichung, Taiwan

[8] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Lab Med, Taipei, Taiwan

[9] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Internal Med, Coll Med, Taipei, Taiwan

[10] Natl Chung Hsing Univ, iEGG, Taichung 402, Taiwan

[11] Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, Anim Biotechnol Ctr, Taichung 402, Taiwan

[12] Natl Chung Hsing Univ, Rong Hsing Res Ctr Translat Med, Taichung 402, Taiwan

[13] Acad Sinica, Inst Cellular & Organism Biol, Marine Res Stn, 23-10 Dahuen Rd, Ilan 262, Taiwan

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 249卷

关键词：

Antimicrobial peptides (AMPs); Peptide drug design; Tilapia piscidins (TPs); Multidrug-resistant (MDR) bacteria; Vibrio vulnificus; Murine wound infection model; CIRCULAR-DICHROISM SPECTRA; VIBRIO-VULNIFICUS; INFECTION; EPINECIDIN-1; MODEL;

D O I：

10.1016/j.ejmech.2023.115131

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Antimicrobial peptides (AMPs) show great promise for clinical applications, but the utility of naturally occurring AMPs is often limited by their stability. Here, we used a rational design approach to improve the characteristics of a pair of inactive peptides, tilapia piscidin 1 and 2 (TP1 and TP2). From each starting peptide, we generated a series of novel derivatives by substituting residues to adjust cationic charge density, percent hydrophobicity and hydrophilicity/hydrophobicity coefficients. This approach yielded a novel peptide, TP2-5 (KKCIA-KAILKKAKKLLKKLVNP), that exhibits significant bactericidal potency, low cytotoxicity and high stability. The designed peptide further showed antibiofilm activity, rapid antibacterial action and a low capacity to induce bacterial resistance. Importantly, we also demonstrated that TP2-5 can protect mice in a Vibrio vulnificus-infected wound model. Therefore, our peptide modification strategy successfully generated a novel AMP with high po-tential for future clinical application.

引用

页数：15