کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356680 981149 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Binding is not enough: Flexibility is needed for photocrosslinking of Lck kinase by benzophenone photoligands
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Binding is not enough: Flexibility is needed for photocrosslinking of Lck kinase by benzophenone photoligands
چکیده انگلیسی

Benzophenone photophores are employed widely for photoaffinity-labeling studies. Photolabeling with benzophenone, however, is hardly a routine experiment. Even when a photoprobe binds to its target, photocrosslinking does not necessarily occur. This is because photolabeling by benzophenone is affected by many factors other than target-binding, such as conformational flexibility of photoligand. Despite the widespread recognition of such complications, there has been no systematic study to assess the relative importance of individual factors that can affect photolabeling efficiency. In order to gain an insight into this problem, we conducted a structure–activity relationship (SAR) study of benzophenone photoligands for Lck kinase, in which photoligands with varying target-binding affinity and conformational flexibility were compared. The study found that binding-affinity, as indicated by kinase inhibitory potency, did not correlate with photolabeling efficiency. Instead, conformational flexibility was found to be the determining factor for efficient photolabeling by our photoligands. Implication of the current findings, in particular, with regard to selection and optimization of benzophenone photoligands, is discussed.

Target-binding is necessary for photoaffinity-labeling, but it does not guarantee successful photocrosslinking. In fact, it is not binding-affinity but conformational flexibility that determines labeling efficiency of our Lck photoprobes.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 19, 1 October 2008, Pages 8824–8829
نویسندگان
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