Microbiology and Biotechnology Letters (한국미생물·생명공학회지)

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Design of Short Indolicidin Analogs with Enhanced Prokaryotic Selectivity

증가된 원핵세포선택성을 가진 짧은 인돌리시딘 유사체의 설계

  • Shin, Song Yub (Department of Cellular & Molecular Medicine, School of Medicine, Chosun University)
  • 신송엽 (조선대학교 의학전문대학원 의학과 세포분자의과학교실)
  • Received : 2012.09.25
  • Accepted : 2012.10.10
  • Published : 2012.12.28
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Abstract

Indolicidin (ID) is a 13-residue Trp-rich antimicrobial peptide (AMP) isolated from bovine neutrophils. In addition to having a high antimicrobial potency, it is also toxic to mammalian cells. To develop novel ID-derived AMPs with shorter lengths and enhanced prokaryotic selectivities (meaning potent antimicrobial activity against bacterial cells without toxicity against mammalian cells) over the parental ID, several ID analogs were designed and synthesized. Finally, 10-residue ID analogs (SI, SI-PA, SI-WF and SI-WL) with much higher prokaryotic selectivity than the parental ID were developed. Our results suggest that the hydrophobic and aromatic amino acids at the central position of the analog SI with the highest prokaryotic selectivity are important for potent antimicrobial activity, but two Pro residues do not affect antimicrobial activity. The order of prokaryotic selectivity for ID and its designed analogs was SI > SI-PA > SI-WF > SI-WL > ID > SI-WA. Taken together, our designed short ID analogs could be developed as therapeutic agents for treating bacterial infections.

인돌리시딘(indolicidin)은 소의 호중구(bovine neutrophils)로 부터 분리된 13개의 아미노산 잔기로 이루어 지고, 트립토판(tryptophan)을 많이 함유한 항균 펩타이드(antimicrobial peptide)이다. 인돌리시딘은 강력한 항균활성과 더불어 mammalian cells에 대해 독성을 나타낸다. 본 연구에서는 인돌리시딘 보다 서열이 짧으며, 보다 증가된 원핵세포 선택성(박테리아세포에 대해 독성을 나타내지만 mammalian cells에 대해서는 독성을 나타내지 않음을 의미함)을 지닌 새로운 짧은 항균 펩타아드를 개발하기 위해, 몇 종의 인돌리시딘 유사체 펩타이드를 설계하고 합성하였다. 결과적으로, 인돌리시딘 보다 서열이 짧으며(10개의 아미노산 잔기로 이루어짐), 증가된 원핵세포선택성을 지닌 4종의 새로운 펩타이드(SI, SI-PA, SI-WF 및 SI-WL)를 개발하였다. 본 연구를 통하여 가장 높은 원핵세포선택성을 나타내는 인돌리시딘 유사체 펩타이드 SI의 항균활성에는 중앙부위에 위치하는 소수성 및 방향족 아미노산이 중요하며, 2군데의 프로린(proline) 잔기는 중요하지 않다는 것을 알았다. 인돌리시딘과 유사체 펩타이드에 대한 원핵세포 선택성은 SI>SI-PA>SI-WF>SI-WL>ID>SI-WA의 순서 이였다. 따라서, 본 연구에서 설계되고 합성한 4종의 인돌리시딘 유사체 펩타이드(SI, SI-PA, SI-WF 및 SI-WL)는 박테리아 감염의 치료제로서 개발될 수 있을 것이다.

Keywords

References

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