İNSAN KANINDAN HEMOGLOBİN UZAKLAŞTIRILMASI İÇİN KRİYOJEL KOLONLARININ HAZIRLANMASI


Doç. Dr. ALİ ARAZ

Tez Türü: Doktora

Tezin Yürütüldüğü Kurum: Hacettepe Üniversitesi, Fen Bilimleri Enstitüsü, Kimya A.B.D., Türkiye

Tez Danışmanı: Adil Denizli

Tezin Onay Tarihi: 2013

Tezin Dili: İngilizce

Desteklendiği Program: Diğer

Özet:

Proteins are vital molecules for the living organisms. They carry out many important physiological metabolic pathways. Therefore they have always been the study of interest. The term proteome defines the large-scale study of proteins including the proteins produced by any organism as well as their modifications made after the synthesis. An evolving field of the proteomics is to identify disease linked novel proteins within the erythrocyte proteins. As in the all proteomic studies of the blood plasma, high abundant proteins in erythrocytes, i.e. hemoglobin and carbonic anhydrase, interfere with the analysis of low abundant and disease related proteins. Thus it is essential to remove these proteins before detailed analysis of cytosolic proteins of erythrocytes. In the previous studies nickel affinity chromatography has been investigated for its efficiency for hemoglobin depletion and shown to be effective for increasing the number of detectable proteins.

In this thesis we aimed the preparation of the metal chelate affinity cryogels for the hemoglobin depletion. PHEMA cryogels are selected as base matrix because of their blood compatibility, osmotic, chemical and mechanical stability. Cryogels are also useful when working with the viscous samples such as blood, thanks to their interconnected macroporous structure. PHEMA cryogels are prepared at -12°C for 24 hours. IDA, the chelating agent, was covalently coupled to PHEMA cryogels after activation with the epichlorohydrin. Then Cu2+, Ni2+, Zn2+ and Co2+ ions were chelated to the IDA-bound cryogels. Characterization of the adsorbent was performed with swelling tests, elemental analysis, FTIR, SEM, surface area measurements and blood compatibility studies. IDA attachment was found as 10.71 mmol/g. Specific surface area of the cryogels was 24.7 m2/g. Swelling degree and porosity of the cryogel was 8.49 g H2O/g and 74.1% for PHEMA and 63.5% for PHEMA-IDA cryogels, respectively. The effect of pH, Hb concentration, and ionic strength was investigated. The depletion of the Hb from hemolysate was shown by SDS-PAGE. The FPLC studies confirmed that the prepared adsorbent has a good resolution values with respect to other blood proteins.