Effects of the anti-bacterial peptide cecropin B and its analogs, cecropins B-1 and B-2, on liposomes, bacteria, and cancer cells
Effects of the anti-bacterial peptide cecropin B and its analogs, cecropins B-1 and B-2, on liposomes, bacteria, and cancer cells
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DOI：
10.1016/s0304-4165(97)00024-x
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发表时间：
1997-08-29
影响因子：
3
通讯作者：
Chan, SC
中科院分区：
文献类型：
--
作者：
Chen, HM;Wang, W;Chan, SC
已经合成了天然抗菌肽天蚕素B（CB）的定制类似物；天蚕素B - 1（CB - 1）是通过用CB的N端序列（包含5个赖氨酸残基的第1到10位）替换C端片段（第26到35位残基）构建的。第二种类似物CB - 2与CB - 1相同，只是在Pro - 24和Ala - 25之间插入了一个甘氨酸 - 脯氨酸残基对。这些肽被用于研究它们的抗脂质体、抗菌和抗癌活性。根据半数致死剂量（DL50）分析，当使用类似物而非天然CB时，抗脂质体活性的强度降低了2到3倍。同样，根据最低抑菌浓度（LC）测量，这些类似物对某些细菌的效力比CB低约2到4倍。相比之下，根据半数抑制浓度（IC50）测量，在白血病癌细胞上，CB - 1和CB - 2的效力比天然CB高约2到3倍。根据圆二色性（CD）测量，所有的CB、CB - 1和CB - 2肽都具有相当的螺旋含量。这些结果表明，设计的具有额外阳离子残基的阳离子裂解肽在破坏脂质体和杀死细菌方面效果较差，但在裂解癌细胞方面更有效。对这些观察结果的可能解释进行了讨论。（C）1997年爱思唯尔科学出版社（Elsevier Science B.V.）
Custom designed analogs of the natural anti-bacterial peptide cecropin B (CB) have been synthesized; cecropin B-1 (CB-1) was constructed by replacing the C-terminal segment (residues 26 to 35) with the N-terminal sequence of CB (positions 1 to 10 which include five lysine residues). The second analog, CB-2, is identical to CB-1 except for the insertion of a Gly-Pro residue pair between Pro-24 and Ala-25. These peptides were used to investigate their anti-liposome, anti-bacterial and anti-cancer activities. The strength of anti-liposome activity is reduced two-to three-fold when the analogs are used instead of natural CB based on DL50 analysis. Similarly, the potency of these analogs on certain bacteria is about two-to four-fold lower than those of CB based on LC measurements. In contrast, on leukemia cancer cells, the potency of CB-1 and CB-2 is about two-to three-fold greater than that of natural CB based on IC50 measurements. All CB, CB-1 and CB-2 peptides have comparable helix contents according to CD measurements. These results indicate that the designed cationic lytic peptides, having extra cationic residues, are less effective in breaking liposomes and killing bacteria but mon effective in lysing cancer cells. The possible interpretations for these observations are discussed. (C) 1997 Elsevier Science B.V.