Chen Po-Wen, Shyu Ching-Ling, Mao Frank C
Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan 40227, Republic of China.
Am J Vet Res. 2003 Sep;64(9):1088-92. doi: 10.2460/ajvr.2003.64.1088.
OBJECTIVE-To design short and potent analogs of bovine lactoferricin by use of the concepts of lipophilic bulk and cationic charge. SAMPLE POPULATION-5 synthetic peptides of bovine lactoferricin.
Antibacterial peptides were constructed by synthesizing several decapeptides rich in arginine and tryptophan. Basic residues of bovine lactoferricin (bLf 20-29; residues 20 to 29) were modified by substitution with arginine or lysine and nonbasic residues were modified by substitution with tryptophan, phenylalanine, or isoleucine. Synthetic peptides of bovine lactoferrin (LFB) were designated as LFB-RW (RRWWWRWRRW), LFB-KW (KKWWWKWKKW), LFB-RWa (RRWWRRWRRW), LFB-RF (RRFFFRFRRF), and LFB-RI (RRIIIRWRRI), where R, K, W, F, and I stand for arginine, lysine, tryptophan, phenylalanine, and isoleucine, respectively. Peptides were evaluated by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis.
LFB-RW, LFB-KW, and LFB-RWa possessed equivalent potency as bLf 20-29 against E coli. LFB-RW and LFB-RWa had a 2-fold increase in growth-inhibitory and bactericidal activity against S aureus, compared with bLf 20-29. LFB-RI had the lowest MIC value against E coli among the peptides but lost bactericidal activity. LFB-RW and LFB-KW had stronger bactericidal activities against S aureus or E faecalis, respectively, as well as E coli than the other synthetic peptides. LFB-RF also had antibacterial activity, but this was 2-fold less than that of LFB-RW, as determined by MIC and MBC values.
In construction of potent antibacterial peptides, inclusion of arginine, lysine, tryptophan, or isoleucine residues enhances effectiveness against certain bacteria, as measured by MIC or MBC values.
目的——利用亲脂性基团和阳离子电荷的概念设计牛乳铁蛋白素的短而有效的类似物。样本群体——5种牛乳铁蛋白素的合成肽。
通过合成几种富含精氨酸和色氨酸的十肽来构建抗菌肽。牛乳铁蛋白素（bLf 20 - 29；第20至29位氨基酸残基）的碱性残基用精氨酸或赖氨酸替代进行修饰，非碱性残基用色氨酸、苯丙氨酸或异亮氨酸替代进行修饰。牛乳铁蛋白（LFB）的合成肽被命名为LFB - RW（RRWWWRWRRW）、LFB - KW（KKWWWKWKKW）、LFB - RW a（RRWWRRWRRW）、LFB - RF（RRFFFRFRRF）和LFB - RI（RRIIIRWRRI），其中R、K、W、F和I分别代表精氨酸、赖氨酸、色氨酸苯丙氨酸和异亮氨酸。通过测定它们对大肠杆菌、金黄色葡萄球菌和粪肠球菌的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）来评估这些肽。
LFB - RW、LFB - KW和LFB - RW a对大肠杆菌的效力与bLf 20 - 29相当。与bLf 20 - 29相比，LFB - RW和LFB - RW a对金黄色葡萄球菌的生长抑制和杀菌活性提高了2倍。LFB - RI在这些肽中对大肠杆菌的MIC值最低，但失去了杀菌活性。LFB - RW和LFB - KW分别对金黄色葡萄球菌或粪肠球菌以及大肠杆菌具有比其他合成肽更强的杀菌活性。LFB - RF也具有抗菌活性，但根据MIC和MBC值测定，其活性比LFB - RW低2倍。
在构建有效的抗菌肽时，通过MIC或MBC值测定，包含精氨酸、赖氨酸、色氨酸或异亮氨酸残基可增强对某些细菌的有效性。
