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

Li Li; Zuxian Xu; Ruipin Cao; Jiaxin Li; Chang-Jer Wu; Yinglu Wang; Hu Zhu

doi:10.1016/j.isci.2023.107048

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

iScience. 2023 Jun 7;26(7):107048. doi: 10.1016/j.isci.2023.107048. eCollection 2023 Jul 21.

Authors

Li Li¹, Zuxian Xu¹, Ruipin Cao¹, Jiaxin Li¹, Chang-Jer Wu², Yinglu Wang¹, Hu Zhu^{1

3}

Affiliations

¹ Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Provincial Key Laboratory of Polymer Materials, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou 350007, China.
² Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan.
³ College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou 362000, China.

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.

Keywords: Bacteriology; Biomolecules; Microbiology.