Unknown

Dataset Information

0

Modification Strategy of D-leucine Residue Addition on a Novel Peptide from Odorrana schmackeri, with Enhanced Bioactivity and In Vivo Efficacy.


ABSTRACT: Brevinins are a well-characterised, frog-skin-derived, antimicrobial peptide (AMP) family, but their applications are limited by high cytotoxicity. In this study, a wild-type des-Leu2 brevinin peptide, named brevinin-1OS (B1OS), was identified from Odorrana schmackeri. To explore the significant role of the leucine residue at the second position, two variants, B1OS-L and B1OS-D-L, were designed by adding L-leucine and D-leucine residues at this site, respectively. The antibacterial and anticancer activities of B1OS-L and B1OS-D-L were around ten times stronger than the parent peptide. The activity of B1OS against the growth of Gram-positive bacteria was markedly enhanced after modification. Moreover, the leucine-modified products exerted in vivo therapeutic potential in an methicillin-resistant Staphylococcus aureus (MRSA)-infected waxworm model. Notably, the single substitution of D-leucine significantly increased the killing speed on lung cancer cells, where no viable H838 cells survived after 2 h of treatment with B1OS-D-L at 10 μM with low cytotoxicity on normal cells. Overall, our study suggested that the conserved leucine residue at the second position from the N-terminus is vital for optimising the dual antibacterial and anticancer activities of B1OS and proposed B1OS-D-L as an appealing therapeutic candidate for development.

SUBMITTER: Yao A 

PROVIDER: S-EPMC8473181 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7472354 | biostudies-literature
| S-EPMC7800420 | biostudies-literature
| S-EPMC5408667 | biostudies-literature
| S-EPMC5792174 | biostudies-literature
| S-EPMC4578928 | biostudies-literature
| S-EPMC3566010 | biostudies-literature
| S-EPMC3475718 | biostudies-literature
| S-EPMC4166900 | biostudies-literature
| S-EPMC4671089 | biostudies-literature
| S-EPMC6151381 | biostudies-literature