کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1930015 1536784 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity
چکیده انگلیسی

While gemcitabine (2′-2′-difluoro-2′-deoxycytidine, dFdC) displays wide-ranging antineoplastic activity as a single agent, variable response rates and poor intracellular metabolism often limit its clinical efficacy. In an effort to enhance dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide. Our goal was to evaluate whether the created fusion could induce beneficial, functional changes toward dFdC, expedite dFdC conversion to its active antimetabolites and consequently amplify cell dFdC sensitivity. While kinetic analyses revealed the UCMK/dCK fusion enzyme to possess both native activities, the fusion rendered cells sensitive to the cytotoxic effects of dFdC at the same level as dCK expression alone. These results suggest that increased wild-type UCMK expression does not provide a significant enhancement in dFdC-mediated cytotoxicity and may warrant the implementation of studies aimed at engineering UCMK variants with improved activity toward gemcitabine monophosphate.


► Goal was to enhance dFdC cytotoxicity by the creation of a UCMK/dCK fusion enzyme.
► The UCMK/dCK fusion enzyme possesses both native activities.
► The fusion renders cells equally sensitive to dFdC relative to dCK expression alone.
► Dual activities of fusion not sufficient to augment cell dFdC sensitivity in vitro.
► Data may warrant the implementation of UCMK mutagenesis studies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 416, Issues 1–2, 9 December 2011, Pages 199–204
نویسندگان
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