Site-specific grafting on titanium surfaces with hybrid temporin antibacterial peptides†,Journal of Materials Chemistry B

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Site-specific grafting on titanium surfaces with hybrid temporin antibacterial peptides†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-02-19 00:00:00 , DOI: 10.1039/c8tb00051d
Nicolas Masurier _{1,

2,

3,

4,

5} , Jean-Baptiste Tissot _{3,

4,

5,

6,

7} , Douae Boukhriss _{1,

2,

3,

4,

5} , Said Jebors _{1,

2,

3,

4,

5} , Coline Pinese _{1,

2,

3,

4,

5} , Pascal Verdié _{1,

2,

3,

4,

5} , Muriel Amblard _{1,

2,

3,

4,

5} , Ahmad Mehdi _{3,

4,

5,

6,

7} , Jean Martinez _{1,

2,

3,

4,

5} , Vincent Humblot _{3,

8,

9,

10,

11} , Gilles Subra _{1,

2,

3,

4,

5}

Affiliation

Relying on a membrane-disturbing mechanism of action and not on any intracellular target, antimicrobial peptides (AMP) are attractive compounds to be grafted on the surface of implantable materials such as silicone catheters or titanium surgical implants. AMP sequences often display numerous reactive functions (e.g. amine, carboxylic acid) on their side chains and straightforward conjugation chemistries could lead to uncontrolled covalent grafting, random orientation, and non-homogenous density. To achieve an easy and site specific covalent attachment of unprotected peptides on titanium surfaces, we designed hybrid silylated biomolecules based on the temporin-SHa amphipathic helical antimicrobial sequence. With the grafting reaction being chemoselective, we designed five analogues displaying the silane anchoring function at the N-ter, C-ter or at different positions inside the sequence to get an accurate control of the orientation. Grafting density calculations were performed by XPS and the influence of the orientation of the peptide on the surface was clearly demonstrated by the measure of antimicrobial activity. Temporin amphipathic helices are described to permeabilize the bacterial membrane by interacting in a parallel orientation with it. Our results move in the direction of this mechanism as the selective grafting of hybrid temporin 2 through a lysine placed at the center of the peptide sequence, resulted in better biofilm growth inhibition of E. coli and S. epidermis than substrates in which temporins were grafted via their C- or N-terminus.

中文翻译：

杂色temporin抗菌肽在钛表面上的定点嫁接†

依靠膜干扰机制而不是任何细胞内靶标，抗菌肽（AMP）是有吸引力的化合物，可以移植到可植入材料（如硅胶导管或钛外科植入物）的表面。AMP序列通常显示许多反应功能（例如，胺，羧酸）在其侧链上的化学键合和直接的共轭化学作用可能导致不受控制的共价接枝，无规取向和不均匀的密度。为了实现不受保护的肽在钛表面上的简便且特定位点共价连接，我们基于temporin-SHa两亲性螺旋抗菌序列设计了杂化的甲硅烷基化生物分子。由于接枝反应是化学选择性的，我们设计了五个类似物，它们在N-末端，C-末端或序列内部的不同位置显示硅烷锚定功能，以精确控制方向。通过XPS进行了接枝密度计算，并且通过抗菌活性的测量清楚地证明了肽的取向在表面上的影响。Temporin两亲性螺旋被描述为通过与细菌膜平行取向相互作用来透化细菌膜。我们的结果朝着这种机理的方向发展，因为杂种临时蛋白的选择性嫁接通过在肽序列的中心放置赖氨酸2，比通过temporin的C-或N-末端嫁接temporins的底物对大肠杆菌和表皮链球菌的生物膜生长的抑制作用更好。

更新日期：2018-02-19

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