کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10883560 1078451 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Helix mimetics: Recent developments
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوفیزیک
پیش نمایش صفحه اول مقاله
Helix mimetics: Recent developments
چکیده انگلیسی
The development of protein-protein interaction (PPIs) inhibitors represents a challenging goal in chemical biology and drug discovery. PPIs are problematic targets because they involve large surfaces with less well defined features and recognition motifs that are less amenable to conventional experimental and computational ligand discovery methodologies. α-Helix mediated PPIs represent a sub group with a clearly defined interface and thus may be more amenable to the development of generic ligand discovery methods. Indeed, this is borne out in numerous studies using peptides covalently constrained into a helical conformation resulting in improvement of myriad biophysical and cellular properties. It is however desirable to have small molecule alternatives: a helix mimetic (proteomimetic) is a generic small molecule scaffold that projects functional groups in a similar spatial orientation so as to mimic the presentation of key amino acid side chains from the helix that mediates the PPI. The first true example of a helix mimetic was described over a decade ago however this approach has not yet been elaborated to the extent that it receives similar levels of attention to constrained peptides. This review explores recent significant developments in the area of small molecule α-helix mimetics and provides a critical overview of success stories, potential limitations of the approach, and areas for future development.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Progress in Biophysics and Molecular Biology - Volume 119, Issue 1, October 2015, Pages 33-40
نویسندگان
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