| Autor: |
Gasu EN; Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Mensah JK; Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Borquaye LS; Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.; Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. |
| Abstrakt: |
The chemophysical properties of a peptide isolated from Olivancillaria hiatula were combined with computational tools to design new antimicrobial peptides (AMPs). The in silico peptide design utilized arbitrary sequence shuffling, AMP sequence prediction and alignments such that putative sequences mimicked those of proline-rich AMPs (PrAMPs) and were potentially active against bacteria. Molecular modelling and docking experiments were used to monitor peptide binding to some intracellular targets like bacteria ribosome, DnaK and LasR. Peptide candidates were tested in vitro for antibacterial and antivirulence activities. Chemophysical studies of peptide extract suggested hydrophobic, acidic and proline-rich peptide properties. The amino acid signature of the extract matched that of AMPs that inhibit intracellular targets. Two of the designed PrAMP peptides (OhPrP-3 and OhPrP-5) had high affinity for the ribosome and DnaK. OhPrP-1, 2 and 4 also had favorable interactions with the biomolecular targets investigated. Peptides had bactericidal activity at the minimum inhibitory concentration against Pseudomonas aeruginosa . The designed peptides docked strongly to LasR suggesting possible interference with quorum sensing, and this was corroborated by in vitro data where sub-inhibitory doses of all peptides reduced pyocyanin and pyoverdine expression. The designed peptides can be further studied for the development of new anti-infective agents. |
