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Synthetic peptides with selective affinity for apoptotic cells
Kristy M DiVittorio1, James R Johnson, Emma Johansson
1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Organic & Biomolecular Chemistry
|May 12, 2006
Summary
New fluorescent peptides detect cell apoptosis by binding anionic phosphatidylserine (PS). These zinc coordination complexes offer an alternative to annexin V for apoptosis detection in research applications.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Anionic phosphatidylserine (PS) exposure on the plasma membrane outer leaflet signals early/intermediate apoptosis.
- Annexin V is the standard reagent for detecting cell surface PS, but alternative methods are needed for specific applications.
Purpose of the Study:
- To develop and characterize novel peptide-based reagents that can detect anionic phosphatidylserine (PS) on apoptotic cells.
- To explore zinc 2,2'-dipicolylamine (Zn2+-DPA) coordination complexes as functional mimics of annexin V for apoptosis sensing.
Main Methods:
- Synthesis of fluorescently-labelled tri- and pentapeptides incorporating Zn2+-DPA side chains.
- Assessment of selective binding of these peptides to anionic vesicle membranes.
- Utilizing fluorescein-labelled peptides for detecting apoptotic cells via fluorescence microscopy and flow cytometry.
Main Results:
- The designed peptides selectively bind to anionic vesicle membranes, indicating their ability to target PS-rich surfaces.
- Fluorescein-labelled peptide conjugates successfully detected apoptotic cells using fluorescence microscopy and flow cytometry.
- The Zn2+-DPA coordination complexes demonstrated a capacity to mimic the function of annexin V in sensing apoptosis.
Conclusions:
- Rationally designed Zn2+-DPA peptide complexes represent a viable alternative to annexin V for detecting anionic PS on apoptotic cells.
- These novel fluorescent probes offer a new tool for apoptosis research, adaptable to various detection platforms.
- The findings support the potential of coordination complexes in developing targeted molecular probes for cell biology studies.