Abstract：
:Bicalutamide (BCT), a drug used in the treatment of prostate cancer, antagonises the actions of androgens, at the receptor level, thereby inhibiting the growth of prostate tumours. Alpha-2-macroglobulin (α2M), a pan-proteinase inhibitor, inhibits proteinase, regardless of specificity and catalytic mechanism. α2M is deficient in patients of advanced prostate cancer with bone metastases. Our studies explored the interaction of BCT with α2M and analysed the BCT induced structural alteration to the α2M. The result suggests that BCT decreases the antiproteolytic potential and causes structural and functional change in human α2M. UV-visible absorption spectroscopy confirms the formation of α2M-BCT complex. Fluorescence analysis shows significant quenching in fluorescence intensity of α2M upon binding with BCT. Synchronous fluorescence result suggests the interaction of BCT with α2M changed the microenvironment around tyrosine residues. Secondary structure of α2M also undergoes a slight change upon complexation with the drug as evident by shift in negative ellipticity in far UV CD spectroscopy. FTIR results confirm the alteration in secondary structure of α2M upon drug interaction. Molecular docking studies show that BCT bind to a monomer of α2M primarily through hydrophobic force. Thermodynamics parameters were determined by isothermal titration calorimetry found that the binding was exothermic in nature.
journal_name
Int J Biol Macromoljournal_title
International journal of biological macromoleculesauthors
Zia MK,Siddiqui T,Ali SS,Ahsan H,Khan FHdoi
10.1016/j.ijbiomac.2018.08.117subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2285-2292issue
Pt Beissn
0141-8130issn
1879-0003pii
S0141-8130(18)32760-0journal_volume
120pub_type
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