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A new peptide with membrane-permeable function derived from human circadian proteins
Tao Peng1, Ying-Hui Liu, Chun-Lei Yang
1Department of Biomedical Engineering, School of Basic Medicine and Forensic, Sichuan University, Chengdu 610041, China.
Acta Biochimica Et Biophysica Sinica
|September 4, 2004
Summary
The human Clock protein DNA-binding peptide (hClock-(35-47)) demonstrates effective cell membrane permeability and translocation, similar to known cell-penetrating peptides. This peptide shows promise as a novel carrier for intracellular and blood-brain barrier delivery.
Area of Science:
- Cell Biology
- Biochemistry
- Neuroscience
Background:
- Cell-penetrating peptides (CPPs) like HIV-1 Tat and Antennapedia facilitate intracellular delivery.
- Understanding novel CPPs is crucial for developing targeted drug delivery systems.
Purpose of the Study:
- To investigate the cell permeability and translocation capabilities of the human Clock protein DNA-binding peptide (hClock-(35-47)).
- To explore the potential of hClock-(35-47) as a carrier for intracellular and blood-brain barrier delivery.
Main Methods:
- Fluorescence microscopy was used to observe peptide uptake in vascular endothelial cells (ECV-304) and neuroglial cells.
- Cellular uptake was analyzed based on incubation time, concentration, temperature, and inhibition by other peptides and heparan sulfate.
- In vivo studies involved carotid artery injection in rats and subsequent brain tissue analysis via fluorescence microscopy.
Main Results:
- hClock-(35-47) exhibited translocation activity comparable to Tat-(48-60).
- Cellular uptake was concentration- and time-dependent, occurring similarly at 4°C and 37°C.
- Uptake was saturable, inhibited by other CPPs and heparan sulfate, indicating a shared internalization pathway.
- In vivo experiments demonstrated hClock-(35-47) translocation across the blood-brain barrier.
Conclusions:
- hClock-(35-47) shares internalization pathways with known cell-penetrating peptides.
- This peptide is capable of crossing the blood-brain barrier.
- hClock-(35-47) presents a promising new carrier for intracellular and central nervous system treatments.