Lysine substitutions convert a bacterial-agglutinating peptide into a bactericidal peptide that retains anti-lipopolysaccharide activity and low hemolytic activity.
Lysine substitutions convert a bacterial-agglutinating peptide into a bactericidal peptide that retains anti-lipopolysaccharide activity and low hemolytic activity.
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DOI：
10.1016/j.peptides.2012.03.017
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发表时间：
2012-06
期刊：
影响因子：
3
通讯作者：
Gorr SU
中科院分区：
文献类型：
--
作者：
Abdolhosseini M;Nandula SR;Song J;Hirt H;Gorr SU
GL13 NH 2是一种细菌凝集肽，来源于唾液蛋白腮腺分泌蛋白（PSP、BPIFA 2、SPLUNC 2、C20 orf70）的序列。该肽凝集革兰氏阴性和革兰氏阳性细菌，并在体外和体内显示抗脂多糖活性。然而，GL13NH2不显示杀菌活性。为了产生具有潜在杀菌活性的更具阳离子性的肽，用赖氨酸残基替换三个氨基酸残基以产生肽GL13K。在这份报告中，GL13 K的抗菌和抗炎活性进行了表征。GL13K失去了凝集细菌的能力，但获得了杀菌活性。用丙氨酸取代GL13 K中的单个氨基酸不能恢复细菌凝集。GL13 K对铜绿假单胞菌、戈登链球菌和大肠杆菌有杀菌作用，但对牙龈卟啉单胞菌无杀菌作用。与GL13 NH2的凝集活性不同，GL13 K对铜绿假单胞菌的杀菌活性在唾液存在下得以保留。GL13 NH 2和GL13 K均表现出抗脂多糖活性。在GL13 K中，这种活性似乎依赖于丝氨酸羟基。GL13K保护小鼠免受脂多糖诱导的脓毒症，并且该肽表现出低水平的溶血，表明其可能适合于体内应用。
GL13NH2 is a bacteria-agglutinating peptide derived from the sequence of the salivary protein parotid secretory protein (PSP, BPIFA2, SPLUNC2, C20orf70). The peptide agglutinates both Gram negative and Gram positive bacteria, and shows anti-lipopolysaccharide activity in vitro and in vivo. However, GL13NH2 does not exhibit bactericidal activity. To generate a more cationic peptide with potential bactericidal activity, three amino acid residues were replaced with lysine residues to generate the peptide GL13K. In this report, the antibacterial and anti-inflammatory activities of GL13K were characterized. GL13K had lost the ability to agglutinate bacteria but gained bactericidal activity. Substitution of individual amino acids in GL13K with alanine did not restore bacterial agglutination. GL13K was bactericidal against Pseudomonas aeruginosa, Streptococcus gordonii and Escherichia coli but not Porphyromonas gingivalis. Unlike the agglutinating activity of GL13NH2, the bactericidal activity of GL13K against Pseudomonas aeruginosa was retained in the presence of saliva. Both GL13NH2 and GL13K exhibited anti-lipopolysaccharide activity. In GL13K, this activity appeared to depend on a serine hydroxyl group. GL13K protected mice from lipopolysaccharide- induced sepsis and the peptide exhibited a low level of hemolysis, suggesting that it may be suitable for in vivo application.
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影响因子：
4.3
作者：
Abdolhosseini, Mahsa;Sotsky, Julie B.;Shelar, Anuradha P.;Joyce, Paul B. M.;Gorr, Sven-Ulrik
通讯作者：
Gorr, Sven-Ulrik
影响因子：
3.9
作者：
Gorr, Sven-Ulrik;Abdolhosseini, Mahsa;Sotsky, Julie
通讯作者：
Sotsky, Julie
影响因子：
5.8
作者：
Gautier, Romain;Douguet, Dominique;Drin, Guillaume
通讯作者：
Drin, Guillaume
影响因子：
4.1
作者：
BEELEY, JG;EASON, R;SNOW, DH
通讯作者：
SNOW, DH
影响因子：
3.9
作者：
Geetha, C;Venkatesh, SG;Gorr, SU
通讯作者：
Gorr, SU