کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162662 | 1114336 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
On the Cellular Uptake and Membrane Effect of the Multifunctional Peptide, TatLK15
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کلمات کلیدی
Membrane translocation - انتقال محفظهTAT - تاتImage analysis - تجزیه و تحلیل تصویرPeptide delivery - تحویل پپتیدcircular dichroism - رنگ تابی دورانیToxicity - سمی بودنFluorescence spectroscopy - فوتولومینسانس یا فلوئورسانس یا فسفرسانسDiffusion - واپخش یا انتشار cell penetrating peptide - پپتید نفوذ سلولیCell - یاخته، سلول
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: On the Cellular Uptake and Membrane Effect of the Multifunctional Peptide, TatLK15 On the Cellular Uptake and Membrane Effect of the Multifunctional Peptide, TatLK15](/preview/png/10162662.png)
چکیده انگلیسی
Recently, the multifunctional peptide TatLK15 resulting from the fusion of the cell penetrating peptide Tat and the amphipathic peptide LK15 was shown to be efficient at mediating siRNA and shRNA delivery in leukemia cells to silence the bcr-abl oncoprotein. The present study focused on TatLK15 peptide cellular uptake and defining conditions for its use within a range of doses exhibiting minimal toxicity. The initial part of the study carried out in solution confirmed that the insertion of a glycine bridge allowed retention of the LK15 α-helicity, and fluorescence correlation spectroscopy did not reveal preferential conformations at the studied concentrations. In the second part, TatLK15 uptake mechanisms appeared peptide dose- and cell line- dependent as well as requiring membrane potential. Below a critical dose, TatLK15 toxicity appeared limited for approximately three hours as demonstrated by the combined use of lactate dehydrogenase release, MTT assays, and time-dependent observation of membrane-impermeant dye uptake using high content screening apparatus. Furthermore, toxicity was observed to occur rapidly at higher peptide doses. Finally, a comparison between TatLK15 and another Tat amphipathic peptide construct suggested that α-helix content should be viewed as a key element in the development of similar peptides. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:293-304, 2014
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 1, January 2014, Pages 293-304
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 1, January 2014, Pages 293-304
نویسندگان
Myasar Alkotaji, Alain Pluen, Egor (Faculty of Life Sciences), Zahra Hamrang, Harmesh Aojula,