세균의 Peptide Deformylase(PDF)를 억제하는 새로운 항균물질의 스크리닝

• 영문명: Screening of New Antibiotics Inhibiting Bacterial Peptide Deformylase (PDF)
• 발행기관: 대한약학회
• 저자명: 곽진환(Jin Hwan Kwak) 김현주(Hyun Joo Kim) 설민정(Min Jeong Seol) 서병선(Byung Sun Suh) 이종국(Jong Kook Lee) 최수영(Soo Young Choi)
• 간행물 정보: 『약학회지』제47권 제3호 (2003년), 184~189쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2003.06.30

영문 초록

Peptide deformylase (PDF) is essential and unique to bacteria, thus making it an attractive target for the discovery of novel antibacterial drugs. PDF deformylates the N-formylmethionine of newly synthesized polypeptides in prokaryotes. In this study, a pdf gene from Staphylococcus aureus 6538p was cloned in pET-14b vector and PDF protein was over-produced in Escherichia coli BL21 (DE3). NH2-terminal His-tagged PDF protein was purified by nickel-nitrilotriacetic acid (Ni-NTA) metal-affinity chromatography. Enzymatic activity of purified 6xHis- tagged PDF was tested on the substrate (formyl-Methionine-Alanine-Serine) by formate dehydrogenase-coupled spectrometric assay of peptide deformylase. For the discovery of new PDF inhibitors from chemical libraries and culture broths of soil bacteria, a target-oriented screening sisters using a 96-well plate was developed. About 3,000 commercial chemical libraries were tested in this screening system, and 2 chemicals (0.07%) among them showed an inhibitory activity against PDF enzyme. This result showed that a new screening system can be used for the discovery of new PDF inhibitors.

키워드

Peptide deformylase(PDF) Formate dehydrogenase(FDH) Formyl-Methionine-Alanine-Serine Antibiotics Screening.