Display Settings:

Format

Send to:

Choose Destination
Bioorg Med Chem. 2008 Oct 1;16(19):8824-9. doi: 10.1016/j.bmc.2008.08.077. Epub 2008 Sep 3.

Binding is not enough: flexibility is needed for photocrosslinking of Lck kinase by benzophenone photoligands.

Author information

  • 1Department of Chemistry, Hunter College of CUNY, 695 Park Avenue, New York, NY 10065, USA. akawamur@hunter.cuny.edu

Abstract

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.

PMID:
18799314
[PubMed - indexed for MEDLINE]
PMCID:
PMC2581794
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk