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Journal of Bacteriology, January 2006, p. 328-334, Vol. 188, No. 1
0021-9193/06/$08.00+0     doi:10.1128/JB.188.1.328-334.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Solution Structure of a Novel Tryptophan-Rich Peptide with Bidirectional Antimicrobial Activity

Shu-Yi Wei,¹ Jiun-Ming Wu,¹ Yen-Ya Kuo,¹ Heng-Li Chen,¹ Bak-Sau Yip,^1,2 Shiou-Ru Tzeng,^3* and Jya-Wei Cheng^1,3*

Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan,¹ Department of Neurology, Hsinchu General Hospital, Hsinchu 300, Taiwan,² Pacgen Biopharmaceuticals Corp., 1730-505 Burrard Street, Vancouver, BC V7X 1M6, Canada³

Received 20 June 2005/ Accepted 4 October 2005

Trp-rich antimicrobial peptides play important roles in the host innate defense mechanisms of many plants, insects, and mammals. A new type of Trp-rich peptide, Ac-KWRRWVRWI-NH₂, designated Pac-525, was found to possess improved activity against both gram-positive and -negative bacteria. We have determined that the solution structures of Pac-525 bound to membrane-mimetic sodium dodecyl sulfate (SDS) micelles. The SDS micelle-bound structure of Pac-525 adopts an -helical segment at residues Trp2, Arg3, and Arg4. The positively charged residues are clustered together to form a hydrophilic patch. The three hydrophobic residues Trp2, Val6, and Ile9 form a hydrophobic core. The surface electrostatic potential map indicates the three tryptophan indole rings are packed against the peptide backbone and form an amphipathic structure. Moreover, the reverse sequence of Pac-525, Ac-IWRVWRRWK-NH₂, designated Pac-525_rev, also demonstrates similar antimicrobial activity and structure in membrane-mimetic micelles and vesicles. A variety of biophysical and biochemical methods, including circular dichroism, fluorescence spectroscopy, and microcalorimetry, were used to show that Pac-525 interacted strongly with negatively charged phospholipid vesicles and induced efficient dye release from these vesicles, suggesting that the antimicrobial activity of Pac-525 may be due to interactions with bacterial membranes.

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* Corresponding author. Mailing address for Shiou-Ru Tzeng: Pacgen Biopharmaceuticals Corp., 1730-505 Burrard Street, Vancouver, BC V7X1M6, Canada. Phone: 886-3-5742763. Fax: 886-3-5738243. E-mail: evetzeng{at}pacgenbiopharm.com. Mailing address for Jya-Wei Cheng: Institute of Biotechnology and Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan. Phone: 886-3-5742763. Fax: 886-3-5738243. E-mail: jwcheng{at}life.nthu.edu.tw.

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Journal of Bacteriology, January 2006, p. 328-334, Vol. 188, No. 1
0021-9193/06/$08.00+0     doi:10.1128/JB.188.1.328-334.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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