拟肽
化学
增殖细胞核抗原
核定位序列
细胞生物学
生物物理学
邻近连接试验
荧光素
细胞生长
生物化学
肽
荧光
生物
受体
物理
量子力学
细胞质
作者
Aimee J. Horsfall,Theresa Chav,Jordan L. Pederick,Zoya Kikhtyak,Bethiney C. Vandborg,Wioleta Kowalczyk,Denis B. Scanlon,Wayne D. Tilley,Theresa E. Hickey,Andrew D. Abell,John B. Bruning
标识
DOI:10.1021/acs.jmedchem.3c00471
摘要
Human proliferating cell nuclear antigen (PCNA) is a critical mediator of DNA replication and repair, acting as a docking platform for replication proteins. Disrupting these interactions with a peptidomimetic agent presents as a promising avenue to limit proliferation of cancerous cells. Here, a p21-derived peptide was employed as a starting scaffold to design a modular peptidomimetic that interacts with PCNA and is cellular and nuclear permeable. Ultimately, a peptidomimetic was produced which met these criteria, consisting of a fluorescein tag and SV40 nuclear localization signal conjugated to the N-terminus of a p21 macrocycle derivative. Attachment of the fluorescein tag was found to directly affect cellular uptake of the peptidomimetic, with fluorescein being requisite for nuclear permeability. This work provides an important step forward in the development of PCNA targeting peptidomimetics for use as anti-cancer agents or as cancer diagnostics.
科研通智能强力驱动
Strongly Powered by AbleSci AI