טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAbdelas Meirav
SubjectInteractions of Metals Corroles with Human Serum Albumin
DepartmentDepartment of Chemistry
Supervisors Professor Zeev Gross
Professor Noam Adir


Abstract

Corroles are aromatic, tetra-pyrrolic synthetic macrocycles, whose inner core contains three protons that can be replaced by metal ions. Corroles are considered as intermediate species between porphyrins and corrins, which are well known members in the group of biologically important molecules. Porphyrins are extensively utilized for identification and treatment of tumors due to their high affinity to tumor cells and strong absorption of light. Recent research revealed that corroles also have high affinity to tumor cells.

 The current research has focused on investigation of interactions between corroles and proteins like Human Serum Albumin (HSA) and heme-proteins (myoglobin and horseradish poeroxidase) for future applications. The novel amphiphilic

 bis-sulfonated corrole and its metal complexes were shown to spontaneously form non-covalent conjugates with HSA: up to 10 corrole molecule associate strongly with HSA, and there is at least one very strong and specific interaction. The assumption is that excess water-soluble corroles enter the large hydrophobic pocket within the protein and form aggregates. Crystals of HSA were obtained after many trials, but due to a high concentration of the protein solution (150-250 mg/mL), the solution around the crystals transformed into gel and the diffraction could only confirm that these crystals were indeed protein. Interactions between heme-protein and corroles were investigated reacting apo-proteins with corroles (reconstitution). The interactions within the conjugates were studied by several spectroscopic methods. In the case of horseradish peroxidase, the protein overexpressed by E. coli formed inclusion bodies; therefore the proteins were folded and refolded in presence of corrole. Crystallization of corrole - reconstituted heme-proteins did not occur, probably due to changes in the tertiary structure.