Characterization of antimicrobial, cytotoxic and anti-endotoxin properties of short peptides with different hydrophobic amino acids at ‘a’ and ‘d’ positions of a heptad repeat sequence
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Azmi, Sarfuddin
Srivastava, Saurabh Mishra, N N Tripathi, J K Shukla, P K Ghosh, J K |
|
| Date |
2013-04-15T09:05:00Z
2013-04-15T09:05:00Z 2013 |
|
| Identifier |
Journal of Medicinal Chemistry, 2013, 56 (3), 924–939
http://hdl.handle.net/123456789/1048 |
|
| Description |
To understand the influence of different hydrophobic amino acids at ‘a’ and ‘d’ positions of a heptad repeat sequence on antimicrobial, cytotoxic and anti-endotoxin properties, four fifteen-residues peptides with leucine (LRP), phenylalanine (FRP), valine (VRP) and alanine (ARP) residues at these positions were designed, synthesized and characterized. Though valine is similarly hydrophobic to leucine and phenylalanine, VRP showed significantly lesser cytotoxicity than LRP and FRP; further, the replacement of leucines with valines at ‘a’ and ‘d’ positions of melittin-heptads drastically reduced its cytotoxicity. However, all four peptides exhibited significant antimicrobial activities that correlate well with their interactions with mammalian and bacterial cell membranes and the corresponding lipid vesicles. LRP most efficiently neutralized the LPS-induced pro-inflammatory mediators like NO, TNF-, and IL-6 in macrophages followed by FRP and VRP, and ARP. The results could be useful for designing short antimicrobial and anti-endotoxin peptides with understanding the basis of their activity.
|
|
| Format |
1801654 bytes
application/pdf |
|
| Language |
en
|
|
| Relation |
CDRI Communication No. 8382
|
|
| Subject |
Synthetic peptides
Heptad repeats Antimicrobial activity Cytotoxic activity Peptide-membrane interactions Anti-endotoxin peptide LPS-induced pro-inflammatory responses |
|
| Title |
Characterization of antimicrobial, cytotoxic and anti-endotoxin properties of short peptides with different hydrophobic amino acids at ‘a’ and ‘d’ positions of a heptad repeat sequence
|
|
| Type |
Article
|
|