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Intact human holo-transferrin interaction with oxaliplatin.
Yuan-Yuan Zhao1, Rupasri Mandal, Xing-Fang Li
1Environmental Health Sciences, Department of Public Health Sciences, Faculty of Medicine and Dentistry, University of Alberta, Canada T6G 2G3.
Rapid Communications in Mass Spectrometry : RCM
|June 15, 2005
Summary
Human holo-transferrin (holo-Tf) non-covalently binds oxaliplatin, forming a stable complex. This interaction suggests holo-Tf could be a potential drug carrier for oxaliplatin delivery in cancer therapy.
Area of Science:
- Biochemistry
- Pharmacology
- Analytical Chemistry
Background:
- Oxaliplatin is a platinum-based chemotherapy drug used to treat colorectal cancer.
- Holo-transferrin (holo-Tf) is the iron-saturated form of the transferrin protein, responsible for iron transport in the blood.
Purpose of the Study:
- To investigate the interaction between intact human holo-transferrin and oxaliplatin.
- To characterize the resulting complex and assess its potential for drug delivery.
Main Methods:
- Nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI-QTOF-MS) was used to determine the molecular weight of the complex.
- Size-exclusion high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) was employed to separate and quantify the complex and its components.
Main Results:
- A (1:1) complex of intact holo-Tf and oxaliplatin was identified with a molecular weight of 80,077 Da.
- HPLC/ICPMS confirmed the formation of the protein-drug complex, showing stable iron (Fe) signals and increasing platinum (Pt) signals over time.
- The binding constant for the holo-Tf-oxaliplatin complex was determined to be 7.7x10(5) M-1, indicating non-covalent binding.
Conclusions:
- Holo-transferrin forms a stable, non-covalently bound complex with oxaliplatin.
- The findings suggest that holo-Tf may serve as a viable carrier for oxaliplatin delivery, potentially improving cancer treatment efficacy.