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Published on: March 25, 2019
Prediction of Protein Targets in Ovarian Cancer Using a Ru-Complex and Carbon Dot Drug Delivery Therapeutic
Maja D Nešić1, Tanja Dučić2, Branislava Gemović3
1Center for Light-Based Research and Technologies COHERENCE, Department of Atomic Physics, Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
Abstract:
We predicted the protein therapeutic targets specific to a Ru-based potential drug and its combination with pristine and N-doped carbon dot drug delivery systems, denoted as RuCN/CDs and RuCN/N-CDs. Synchrotron-based FTIR microspectroscopy (µFTIR) in addition to bioinformatics data on drug structures and protein sequences were applied to assess changes in the protein secondary structure of A2780 cancer cells. µFTIR revealed the moieties of the target proteins' secondary structure changes only after the treatment with RuCN and RuCN/N-CDs. A higher content of α-helices and a lower content of β-sheets appeared in A2780 cells after RuCN treatment. Treatment with RuCN/N-CDs caused a substantial increase in parallel β-sheet numbers, random coil content, and tyrosine residue numbers. The results obtained suggest that the mitochondrion-related proteins NDUFA1 and NDUFB5 are affected by RuCN either via overexpression or stabilisation of helical structures. RuCN/N-CDs either induce overexpression of the β-sheet-rich protein NDUFS1 and affect its random coil structure or interact and stabilise its structure via hydrogen bonding between -NH2 groups from N-CDs with protein C=O groups and -OH groups of serine, threonine, and tyrosine residues. The N-CD nanocarrier tunes this drug's action by directing it toward a specific protein target, changing this drug's coordination ability and inducing changes in the protein's secondary structures and function.
Insights
This study identifies protein targets for a Ruthenium-based drug (RuCN) and its carbon dot delivery systems (RuCN/CDs, RuCN/N-CDs). N-doped carbon dots enhance RuCN
Area of Science:
- Biochemistry
- Materials Science
- Cancer Therapeutics
Background:
- Ruthenium (Ru)-based compounds are explored for cancer therapy.
- Carbon dots (CDs) offer potential as drug delivery systems.
- Understanding drug-target interactions at the protein level is crucial for therapeutic development.
Purpose of the Study:
- To predict and identify protein therapeutic targets for a Ru-based drug (RuCN).
- To investigate the effect of pristine and N-doped carbon dot (N-CD) drug delivery systems on RuCN's interaction with cancer cell proteins.
- To analyze changes in protein secondary structure induced by RuCN and RuCN/N-CDs.
Main Methods:
- Synchrotron-based Fourier-transform infrared microspectroscopy (µFTIR) was used to analyze protein secondary structure changes.
- Bioinformatics data on drug structures and protein sequences were utilized.
- A2780 cancer cells were treated with RuCN, RuCN/CDs, and RuCN/N-CDs.
Main Results:
- RuCN and RuCN/N-CDs altered protein secondary structures in A2780 cells.
- RuCN treatment increased alpha-helices and decreased beta-sheets.
- RuCN/N-CDs significantly increased parallel beta-sheets, random coil content, and tyrosine residues.
- Mitochondrion-related proteins NDUFA1, NDUFB5, and NDUFS1 were identified as potential targets.
- N-CDs modulated RuCN's action, influencing target specificity and protein structure.
Conclusions:
- RuCN affects mitochondrion-related proteins NDUFA1 and NDUFB5.
- RuCN/N-CDs target NDUFS1, potentially through hydrogen bonding interactions.
- N-doped carbon dots enhance RuCN's therapeutic potential by directing it to specific protein targets and altering protein function.
