18 research outputs found
Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1
A BODIPY-embedding miltefosine analog linked to cell-penetrating Tat(48-60) peptide favors intracellular delivery and visualization of the antiparasitic drug
The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption
Improving the Follow-Up of Positive Hemoccult Screening Tests: An Electronic Intervention
Reducing Diagnostic Errors through Effective Communication: Harnessing the Power of Information Technology
A biomimetic approach for enhancing the in vivo half-life of peptides
The tremendous therapeutic potential of peptides has not yet been realized, mainly due to their short in vivo half-life. While conjugation to macromolecules has been a mainstay approach for enhancing the half-life of proteins, the steric hindrance of macromolecules often harms the binding of peptides to target receptors, compromising the in vivo efficacy. Here we report a new strategy for enhancing the in vivo half-life of peptides without compromising their potency. Our approach involves endowing peptides with a small-molecule that binds reversibly to the serum protein, transthyretin. Although there are few reversible albumin-binding molecules, we are unaware of designed small molecules that bind reversibly to other serum proteins and are used for half-life extension in vivo. We show here that our strategy was indeed effective in enhancing the half-life of an agonist for GnRH receptor while maintaining its binding affinity, which was translated into superior in vivo efficacy
Dynamic behavior of DNA topoisomerase IIβ in response to DNA double-strand breaks
DNA topoisomerase II (Topo II) is crucial for resolving topological problems of DNA and plays importantroles in various cellular processes, such as replication, transcription, and chromosome segregation.Although DNA topology problems may also occur during DNA repair, the possible involvement ofTopo II in this process remains to be fully investigated. Here, we show the dynamic behavior ofhuman Topo IIβ in response to DNA double-strand breaks (DSBs), which is the most harmful form ofDNA damage. Live cell imaging coupled with site-directed DSB induction by laser microirradiationdemonstrated rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Detergent extractionfollowed by immunofluorescence showed the tight association of endogenous Topo IIβ with DSB sites.Photobleaching analysis revealed that Topo IIβ is highly mobile in the nucleus. The Topo II catalyticinhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβrecruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycinand decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo IIβin HR-mediated DSB repair. Taken together, these results highlight a novel aspect of Topo IIβ functionsin the cellular response to DSBs