کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2007066 1541741 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibiting the inhibitors: Retro-inverso Smac peptides
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibiting the inhibitors: Retro-inverso Smac peptides
چکیده انگلیسی

Resistance against apoptosis-inducing anti-cancer drugs remains a severe problem in therapy. One reason is the overexpression of inhibitors of apoptosis proteins (IAPs), a group of proteins responsible for the prevention of apoptosis induction by inactivation of initiator caspases. The natural inhibitor of the IAPs is the protein Smac, which impedes the binding to the caspases. Although Smac is a potent inhibitor, Smac peptides are not very stable in vivo and thus not applicable in therapy. Bioinformatical methods were applied to design Smac-derived peptides to break the therapy resistance in IAP high-expressing tumor cells. The exchange of amino acids in the Smac peptides AVPI and AVPF against unnatural amino acids leads to an improvement of the apoptosis sensitivity. The variety of Smac peptides was filtered by computational docking. Moreover, Smac-derived peptides with sufficient binding to the IAPs were tested in IAP-expressing Hodgkin Lymphoma cell lines.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 30, Issue 12, December 2009, Pages 2374–2379
نویسندگان
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