声明
ABSTRACT
摘要
Abbreviations
Table of Contents
Chapter 1
1．Introduction
1．1．Molecular interactions
1．2．Protein-ligand interactions
1．2．1．Covalent bond
1．2．2．Coordination bond
1．2．3．Hydrogen bond
1．2．4．Hydrophobic interactions
1．3．Blood and their important constituents
1．4．Plasma and transporter proteins
1．4．1．Serum albumin
1．5．Dimrence between HSA and BSA
1．6．Biological role of Albumin
1．7．Fluorophore
1．7．1．Types of fluorescence
1．8．Amphotericin B(AmB)
1．8．1．Physicochemical properties
1．8．2．Pharmacokinetics
1．8．3．Mechanism of action
1．8．4．Toxicity
1．9．Paromomycin(PAR)
1．9．1．Physicochemical properties
1．9．2．Pharmacokinetics
1．9．3．Mechanism of action
1．9．4．Toxicity
1．1 0．Tobramycin(TOB)
1．10．1．Physicochemical properties
1．10．2．Pharmacokinetics
1．10．3．Mechanism of action
1．10．4．Toxicity
1．11．Significance of binding investigation assays
1．12．Aims and objectives of the thesis
Chapter 2
2．1．Material and methods
2．1．1．Chemicals and analytical procedure
2．1．2．Fluorescence spectra measurement and quenching titration
2．1．3．Ultraviolet-visible(UV)spectroscopy
2．1．5．Circular Dichroic(CD)determination
2．1．6．Dynamic light scattering(DLS)measurements
2．1．7．Molecular docking
2．1．8．Molecular Dynamics(MD)Simulations
2．1．9．Statistical analysis
Chapter 3
3．1．UV visible spectroscopy
3．2．FTIR spectroscopy
3．3．Circular dichroism measurement
3．4．Transmission electron microscopy
3．5．Dynamic light scattering measurement
3．6．Fluorescence spectroscopy analysis
3．6．1．Gibb’s free energy determination
3．6．2．Drugs marker test
3．6．3．3-D fluorescence analysis
3．7．Computational docking analysis
3．8．MD simulation investigation
3．9．Summary
Chapter 4
4．1．1．Fluorescence analysis and mechanism of quenching
4．1．2．Binding affinity
4．1．3．Thermodynamic parameters calculation
4．1．4．PAR-induced microenvironmental perturbations around HSA fluorophores
4．2．Site markers displacement experiment
4．3．Absorption spectroscopy for HSA-PAR complex system formation
4．4．FT-IR measurements for secondary structural changes
4．5．Conformational analysis by circular dichroic(CD)technique
4．6．Particles size calculation by dynamic light scattering(DLS)method
4．7．Resonance Rayleigh scattering(RRS)analysis for native HSA and HSA-PAR
4．8．Prediction of binding modes for PAR by Molecular docking studies
4．9．Molecular dynamics simulation for stability analysis of the docked complex structure
4．10．Summary
Chapter 5
5．1．UV visible spectroscopy
5．2．FTIR measurements
5．3．Circular dichroism measurement
5．4．Fluorescence spectroscopy measurement
5．4．1．Thermodynamic and binding constants determination
5．4．2．Site probing marker experiment
5．4．3．3-D fluorescence analysis
5．5．HSA-TOB docking analysis
5．6． Analysis of molecular dynamics calculations
5．7． Solvent accessible surface area calculations for free and complex HSA
5．6．Summary
Chapter 6
6．1．Conclusion
6．2．Future Perspectives
6．3．List of Publications
6．4．Muslim Raza(Author)
6．5．Professor Qipeng Yuan(Research supervisor)
6．6．Professor Wei Yun(Research Supervisor)
Acknowledgments
References
