Introduction of cell-selectivity in bovine cathelicidin BMAP-28 by exchanging heptadic isoleucine with the adjacent proline at a non-heptadic position,Peptide Science

当前位置： X-MOL 学术 › Pept. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Introduction of cell-selectivity in bovine cathelicidin BMAP-28 by exchanging heptadic isoleucine with the adjacent proline at a non-heptadic position
Peptide Science ( IF 1.5 ) Pub Date : 2020-10-23 , DOI: 10.1002/pep2.24207
Sarfuddin Azmi _{1,

2} , Neeraj Kumar Verma ₁ , Jitendra Kumar Tripathi ₁ , Saurabh Srivastava ₁ , Devesh Pratap Verma ₁ , Jimut Kanti Ghosh ₁

Affiliation

Bovine cathelicidin, BMAP-28 exhibits potent antimicrobial activity without any cell-selectivity. Considering the role of its C-terminus amino acid residues in its cytotoxic activities, we envisioned to rearrange the amino acids at its C-terminus without altering its composition for designing new cell-selective BMAP-28-analog. Thus an isoleucine residue at 20th position, also an “a” position of its previously identified isoleucine zipper sequence, was exchanged with a proline residue at 19th position. As a result, a remarkable reduction in the hemolytic activity of BMAP-28 toward human red blood cells (hRBCs) was observed without hampering its antibacterial activity in liquid media, and in presence of salts and serum. BMAP-28-analog, BMAP-28M depolarized S. aureus membrane and bacterial membrane-mimetic, PE/PG lipid vesicles similar to BMAP-28 but showed weaker efficacy to depolarize hRBC membrane and mammalian membrane-mimetic, PC/Chol vesicles. Differences in the localization of tryptophan residues of BMAP-28 and BMAP-28M were observed only in PC/Chol vesicles. BMAP-28 induced pores of ~3.4 nm diameter onto hRBCs whereas BMAP-28M showed minor perturbation onto these cells. BMAP-28 and BMAP-28M induced the entry of calcein (size, ~1 nm) and 4.4 kDa FITC-dextran (size, ~2.8 nm) into B. megaterium but not of higher sized fluorescent-dextrans indicating toroidal pore formation onto these bacterial membranes.

中文翻译：

通过在非七肽位置与邻近的脯氨酸交换七异异亮氨酸在牛cathelicidin BMAP-28中引入细胞选择性

牛cathelicidin BMAP-28表现出强大的抗菌活性，而没有任何细胞选择性。考虑到其C末端氨基酸残基在其细胞毒性活性中的作用，我们设想重新排列其C末端的氨基酸而不改变其组成，以设计新的细胞选择性BMAP-28-analog。因此，在第20位的异亮氨酸残基，也是其先前鉴定的异亮氨酸拉链序列的“ a”位，与在第19位的脯氨酸残基交换。结果，观察到BMAP-28对人红细胞（hRBCs）的溶血活性显着降低，而没有在液体介质中以及存在盐和血清的情况下抑制其抗菌活性。BMAP-28类似物，BMAP-28M去极化金黄色葡萄球菌膜和细菌膜模拟PE / PG脂质囊泡类似于BMAP-28，但显示出对hRBC膜和哺乳动物膜模拟PC / Chol囊泡去极化的功效较弱。仅在PC / Chol囊泡中观察到BMAP-28和BMAP-28M色氨酸残基的定位差异。BMAP-28在hRBC上诱导了直径约3.4 nm的孔，而BMAP-28M在这些细胞上显示出较小的扰动。BMAP-28和BMAP-28M诱导钙黄绿素（尺寸约1 nm）和4.4 kDa FITC-葡聚糖（尺寸约2.8 nm）进入巨大芽孢杆菌中，但未引入较大尺寸的荧光葡聚糖，表明在其上形成了环形孔细菌膜。

更新日期：2020-10-23

点击分享查看原文

点击收藏

阅读更多本刊最新论文