Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Endocrinology Division and Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI), CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Biomaterials. 2015 Jul;56:92-103. doi: 10.1016/j.biomaterials.2015.03.046. Epub 2015 Apr 16.
KLD-12 (KLD) is a 12-residue self-assembling peptide that can adopt nano-structures and is known for its tissue-engineering properties. Our objective was to introduce antimicrobial attribute to KLD which would help in preventing secondary infection associated with external application of such tissue engineering materials. Considering the net charge of KLD-12, varying number of cationic arginine residues were added to its N-terminus. KLD variants showed appreciable bactericidal properties without any significant increase in cytotoxicity against tested mammalian cells. Further, these variants adopted β-sheet structures and self-assembled into nano-structures comparable to that of KLD. Interestingly, the KLD variants with two (KLD-2R) and three (KLD-3R) arginine residues added to its N-terminus showed significant osteogenic effect which was comparable or better than the original peptide as evident from the alkaline phosphatase activity assay, mineralized nodule formation and expression of different osteogenic genes. Particularly, application of KLD-2R in rats to the site of a drill-hole (0.8 mm diameter) that was created in the femur metaphysis displayed significantly higher bone regeneration compared to that of KLD. The results demonstrate a simple way to improve biological property of a self-assembling peptide with tissue engineering property.
KLD-12 (KLD) 是一种 12 个残基的自组装肽，可以形成纳米结构，具有组织工程特性。我们的目标是为 KLD 引入抗菌属性，以防止与这些组织工程材料的外部应用相关的二次感染。考虑到 KLD-12 的净电荷，在其 N 端添加了不同数量的阳离子精氨酸残基。KLD 变体表现出相当的杀菌特性，对测试的哺乳动物细胞没有明显增加细胞毒性。此外，这些变体采用 β-折叠结构并自组装成纳米结构，与 KLD 相当。有趣的是，在 KLD 的 N 端添加两个（KLD-2R）和三个（KLD-3R）精氨酸残基的 KLD 变体显示出显著的成骨作用，与原始肽相当或更好，从碱性磷酸酶活性测定、矿化结节形成和不同成骨基因的表达可以明显看出。特别是，将 KLD-2R 应用于大鼠股骨干骺端直径为 0.8 毫米的钻孔部位，与 KLD 相比，骨再生明显增加。结果表明，这是一种简单的方法，可以提高具有组织工程特性的自组装肽的生物学特性。
