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Effects of hydroxyl group in cyclo(Pro-Tyr)-like cyclic dipeptides on their anti-QS activity and self-assembly.


ABSTRACT: We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo(L-Pro-L-Tyr), cyclo(L-Hyp-L-Tyr), and cyclo(L-Pro-L-Phe), against Pseudomonas aeruginosa PAO1. Cyclo(L-Pro-L-Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) suppressed genes in both the las and rhl systems, whereas cyclo(L-Pro-L-Phe) mainly downregulated rhlI and pqsR expression. These cyclic dipeptides interacted with the QS-related protein LasR, with similar binding efficiency to the autoinducer 3OC12-HSL, except for cyclo(L-Pro-L-Phe) which had lower affinity. In addition, the introduction of hydroxyl groups significantly improved the self-assembly ability of these peptides. Both cyclo(L-Pro-L-Tyr) and cyclo(L-Hyp-L-Tyr) formed assembly particles at the highest tested concentration. The findings revealed the structure-function relationship of this kind of cyclic dipeptides and provided basis for our follow-up research in the design and modification of anti-QS compounds.

SUBMITTER: Li L 

PROVIDER: S-EPMC10285644 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Effects of hydroxyl group in cyclo(Pro-Tyr)-like cyclic dipeptides on their anti-QS activity and self-assembly.

Li Li L   Xu Zuxian Z   Cao Ruipin R   Li Jiaxin J   Wu Chang-Jer CJ   Wang Yinglu Y   Zhu Hu H  

iScience 20230607 7


We investigated the influence of hydroxyl groups on the anti-quorum-sensing (anti-QS) and anti-biofilm activity of structurally similar cyclic dipeptides, namely cyclo(<i>L</i>-Pro-<i>L</i>-Tyr), cyclo(<i>L</i>-Hyp-<i>L</i>-Tyr), and cyclo(<i>L</i>-Pro-<i>L</i>-Phe), against <i>Pseudomonas aeruginosa</i> PAO1. Cyclo(<i>L</i>-Pro-<i>L</i>-Phe), lacking hydroxyl groups, displayed higher virulence factor inhibition and cytotoxicity, but showed less inhibitory ability in biofilm formation. Cyclo(<i>  ...[more]

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