Project

Back to overview

Structure-activity relationships in Cu/Zn superoxide dismutase (SOD) and SOD-mimics before and after encapsulation in polymeric nanocontainers

English title Structure-activity relationships in Cu/Zn superoxide dismutase (SOD) and SOD-mimics before and after encapsulation in polymeric nanocontainers
Applicant Palivan Cornelia
Number 115956
Funding scheme Project funding
Research institution Physikalische Chemie Departement Chemie Universität Basel
Institution of higher education University of Basel - BS
Main discipline Physical Chemistry
Start/End 01.04.2007 - 31.03.2010
Approved amount 152'550.00
Show all

Keywords (11)

structure-activity relationship; Cu/Zn superoxide dismutase (SOD); SOD-mimics; triblock copolymers; self-assembly; nanocontainers; wave and pulse- Electron Paramagnetic; Resonance; Electron Paramagnetic Resonance; structure-activity analysis; nanoreactor

Lay Summary (English)

Lead
Lay summary
Reactive oxygen species, such as the superoxide radical anion (O2¯), are responsible for oxidative stress in cells, that has been implicated in the pathogenesis of many cardiovascular and pulmonary diseases. Cu/Zn Superoxide dismutase (Cu/Zn-SOD) is one of the metal proteins which act as an antioxidant enzyme by lowering the steady-state concentration of the superoxide radical anion (O2¯), its active site being located in the region of the metal centre.The present study combines inorganic, bioorganic, physical chemistry and polymers chemistry to obtain a better understanding of the link between the structure and the role of the metal binding region of Cu/Zn-SOD or SOD-mimics and to design new hybrid materials after their encapsulation in polymer nanocontainers. The project is oriented in two directions:1.A global structure-activity analysis applied to all classes of copper complexes already proposed as SOD-mimics in order to establish a structural model for high SOD activity. The question we address is "Is there a general relationship between geometrical parameters describing the environment of the metal for SOD-mimics, or are there a number of specific ligand arrangements that induce a high level of biological activity?"2.We designed and tested the first antioxidant nanoreactor based on encapsulation of Cu,Zn superoxide dismutase in amphiphilic copolymer nanovesicles whose membranes are oxygen permeable. The function of this antioxidant nanoreactor was tested by pulse radiolysis which demonstrated that superoxide dismutase remains active inside the nanovesicles and detoxifies the superoxide radical in situ. The membrane of our triblock copolymer nanovesicles plays a double role, both to shield the sensitive protein and selectively to let superoxide and dioxygen penetrate to its inner space. This hybrid system provides a selective shielding of sensitive enzymes from proteolytic attack and therefore a new direction for developing drug delivery applications.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
124406 ANTIOXIDANT NANOREACTORS BASED ON CO-ENCAPSULATION OF ENZYMES IN POLYMERIC VESICLES 01.06.2009 Project funding
129968 STRUCTURE-ACTIVITY ANALYSIS OF SOD-MIMICS AND THEIR ENCAPSULATION IN NANOREACTORS 01.04.2010 Project funding
140302 PROTEIN-POLYMER SUPRAMOLECULAR ASSEMBLIES IN THE DESIGN OF ANTIOXIDANT NANOREACTORS AND PROCESSORS 01.06.2012 Project funding

-