초록

본 연구를 통하여 저분자 화합물 및 펩타이드 미메틱을 이용하여 polo-like kinase 1 (Plk1)의 polo-box domain (PBD)의 저해제를 개발하는데 성공 하였으며. 이러한 저해제 를 이용하여 PLK1의 생물학적 기작 규명하였다. 이러한 생물학적 규명은 새로운 개념의 항암제 개발에 많은 정보를 줄 것으로 기대 된다.

Abstract ▼

Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and chara

Recent progress in the development of peptide-derived Polo-like kinase (Plk1) polo-box domain (PBD) inhibitors has led to the synthesis of multiple peptide ligands with high binding affinity and selectivity. However, few systematic analyses have been conducted to identify key Plk1 residues and characterize their interactions with potent Plk1 peptide inhibitors. We performed systematic deletion analysis using the most potent 4j peptide and studied N-terminal capping of the minimal peptide with diverse organic moieties, leading to the identification of the peptidomimetic 8 (AB-103) series with high improved binding affinity and selectivity. To evaluate the bioavailability of short peptidomimetic ligands, PEGylated 8 series were synthesized and incubated with HeLa cells to test for cellular uptake, anti-proliferative activity, and Plk1 kinase inhibition. Finally, crystallographic studies of the Plk1 PBD in complex with peptidomimetics 8 and 22 (AB-103-5) revealed the presence of 2 hydrogen bond interactions responsible for their improved binding affinity and selectivity.

목차 Contents

• 표지 ... 1
• 제출문 ... 2
• 요약문 ... 3
• SUMMARY ... 4
• CONTENTS ... 5
• 제1장 연구개발과제의 개요 ... 6
• 제2장 국내외 기술개발 현황 ... 9
• 제3장 연구개발 범위 ... 11
• 제3장 연구 내용 및 결과 ... 17
• 제5장 목표달성도 및 관련분야에의 기여도 ... 45
• 제6장 연구개발결과의 활용계획 ... 46
• 제7장 참고문헌 ... 47
• 끝페이지 ... 49