Amino Acids

, Volume 44, Issue 4, pp 1215–1224 | Cite as

Rational design of cationic antimicrobial peptides by the tandem of leucine-rich repeat

  • Q. Q. Ma
  • Y. F. Lv
  • Y. Gu
  • N. Dong
  • D. S. Li
  • A. S. Shan
Original Article

Abstract

Antimicrobial peptides represent ancient host defense effector molecules present in organisms across the evolutionary spectrum. Lots of antimicrobial peptides were synthesized based on well-known structural motif widely existed in a variety of lives. Leucine-rich repeats (LRRs) are sequence motifs present in over 60,000 proteins identified from viruses, bacteria, and eukaryotes. To elucidate if LRR motif possesses antimicrobial potency, two peptides containing one or two LRRs were designed. The biological activity and membrane–peptide interactions of the peptides were analyzed. The results showed that the tandem of two LRRs exhibited similar antibacterial activity and significantly weaker hemolytic activity against hRBCs than the well-known membrane active peptide melittin. The peptide with one LRR was defective at antimicrobial and hemolytic activity. The peptide containing two LRRs formed α-helical structure, respectively, in the presence of membrane-mimicking environment. LRR-2 retained strong resistance to cations, heat, and some proteolytic enzymes. The blue shifts of the peptides in two lipid systems correlated positively with their biological activities. Other membrane-peptide experiments further provide the evidence that the peptide with two LRRs kills bacteria via membrane-involving mechanism. The present study increases our new understanding of well-known LRR motif in antimicrobial potency and presents a potential strategy to develop novel antibacterial agents.

Keywords

Antimicrobial peptides Leucine-rich repeat Membrane–peptide interaction 

Abbreviations

AMP

Antimicrobial peptide

LRR

Leucine-rich repeat

diSC3(5)

3-3-Dipropylthiadicarbocyanine-iodide

MIC

Minimum inhibitory concentration

MHC

Minimal hemolytic concentration

CD

Circular dichroism

PC

Phosphatidylcholine

PE

Phosphatidylethanolamine

PG

Phosphatidylglycerol

NPN

N-phenyl-1-naphthylamine

MH

Mueller–Hinton

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Q. Q. Ma
    • 1
  • Y. F. Lv
    • 1
  • Y. Gu
    • 1
  • N. Dong
    • 1
  • D. S. Li
    • 2
  • A. S. Shan
    • 1
  1. 1.Institute of Animal NutritionNortheast Agricultural UniversityHarbinChina
  2. 2.College of Life ScienceNortheast Agricultural UniversityHarbinChina

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