An Anti-microbial Peptide Derivative of Flesh Fruit Fly Mimics Secretory Signal Sequence and Inhibits Signal Peptidase-I in the Export Pathway

  • Naheed N. Kaderbhai
  • Tasawar Khan
  • Mustak A. Kaderbhai


Combinatorial search of the antimicrobial peptide R7SLCLLHCRLK from flesh fruit fly yielded a substantially more active peptide of the sequence KLKL5KLK-NH2 that had signal sequence character as revealed by Neural-network survey. Bioinformatics survey of KLKLnKLK revealed a sigmoidal relationship between SSP and the intervening Leu stretch. Synthetic enantiomeric KLKLnKLK peptides inhibited Escherichia coli signal peptidase-I, in vitro, in correlation with their SSPs; KLKL6(7)KLK exterted maximum inhibition. Both (l)-and (d)-forms were bactericidal to Gram-positive and Gram-negative bacteria. However, the protease-resistant (d)-KLKL6KLK-NH2 proved more potent than (d)-KLKL6KLK-NH2 at inhibiting the bacterial protein secretion prior to inducing bacterial lysis. Kinetic analyses of the interaction of these peptides with the signal peptidase-I revealed competitive inhibition with Ki of 10 μM and 35 μM for the (d)- and (l)-forms, respectively. The left and right-handed helicity of the respective peptides assessed by CD concurs with their probable interaction at the active site of signal peptidase-I.


Antimicrobial peptides Signal peptidase-I Signal sequence Protein secretion 



Anti-microbial peptide


Grand average hydropathicity


Minimum inhibitory concentration


Signal sequence


Signal sequence probability



We are grateful to Wales Research and Innovation for financial support. This work was in part supported by a grant from R & D Systems for the development of visually-based PINK protein secretion system. We thank Jim Heald for his continued technical support. We thank Prof Shunzi Natori (Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-Ku, Tokyo 113, Japan) for gift of peptides used in the early part of this work.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Naheed N. Kaderbhai
    • 1
  • Tasawar Khan
    • 1
  • Mustak A. Kaderbhai
    • 1
  1. 1.Institute of Biological Sciences, Cledwyn BuildingAberystwyth UniversityCeredigionUK

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