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  • 02월 28일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제123회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Peptidomimetics Targeting Polo-Box Domain of Polo-like kinase 1

2019년 2월 7일 14시 54분 46초
LIFE1-4 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 17시 : 10분
Life Chemistry - Recent Trends in Biopharmaceuticals Research
저자 및
Jeong-kyu Bang
Korea Basic Science Institute, Korea
The serine/threonine kinase Polo-like kinase 1 (Plk1) is a regulator of multiple stages of mitotic progression. Several Plk1 kinase inhibitors have been uniformly demonstrated to induce mitotic arrest and apoptosis of cancer cells in vitro and in vivo. The PBD is unique to the family of PLKs and therefore it is ideally suited for studying the feasibility of inhibiting PLK1 by selectively influencing its protein-protein interaction. We have tried to develop the short peptidomimetic Plk1 PBD inhibitors with enhanced binding affinity and selectivity against Plk1 PBD from closely related Plk2 and Plk3. To achieve the desired short peptidomimetic agents, a systematic deletion and the N-terminal capping using diverse organic moieties were effected over the most potent 4j peptide, which led to the identification of AB-103 series with improved binding affinity and selectivity. In addition, AB-103 and their PEG-conjugated compounds were evaluated against their cellular uptake, anti-proliferation and Plk1 kinase inhibition by direct incubation with HeLa cells. Finally, improved binding affinity and selectivity of our derived compounds are explained by crystallographic evidences