Variants of self-assembling peptide, KLD-12 that show both rapid fracture healing and antimicrobial properties.
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.
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Jitendra K
JK
Tripathi
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.
Subhashis
S
Pal
Electron Microscopy Unit, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Bhanupriya
B
Awasthi
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Amit
A
Kumar
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Anshika
A
Tandon
Electron Microscopy Unit, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India.
Kalyan
K
Mitra
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. Electronic address: n_chattopadhyay@cdri.res.in.
Naibedya
N
Chattopadhyay
Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226 031, India. Electronic address: jk_ghosh@cdri.res.in.
Jimut Kanti
JK
Ghosh
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration; D002412:Cations; D004912:Erythrocytes / Q000166:cytology; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005269:Femur / Q000473:pathology; D017102:Fracture Healing; D006461:Hemolysis; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D010012:Osteogenesis; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D002412:Cations; C000604947:KLD-2R peptide; D008055:Lipids; D010455:Peptides; D001120:Arginine; D000469:Alkaline Phosphatase
Antimicrobial and cytotoxic activity of peptides; Osteogenic peptides; Peptide biomaterials; Peptide nano-structures; Self-assembling peptide; Tissue engineering properties of peptides