Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins αVβ3 and α5β1
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The human pathogen Helicobacter pylori that may cause different gastric diseases exploits integrins for infection of gastric cells. The H. pylori protein CagL present on the outer region of the type IV secretion pilus contains an RGD sequence (-Arg-Gly-Asp-) that enables binding to cells presenting integrins α5β1 and αVβ3. This interaction can be inhibited with conformationally designed cyclic RGD peptides derived from the CagL epitope -Ala-Leu-Arg-Gly-Asp-Leu-Ala-. The inhibition of the CagL–αVβ3 interaction by different RGD peptides strongly suggests the importance of the RGD motif for CagL binding. CagL point mutants (RAD, RGA) show decreased affinity to integrin αVβ3. Furthermore, structure–activity relationship studies with cyclic RGD peptides in a spatial screening approach show the distinct influence of the three-dimensional arrangement of RGD motif on the ability to interfere with this interaction. Resulting from these studies, similar structural requirements for the CagL epitope as previously suggested for other ligands of integrin αVβ3 are proposed.
KeywordsCagL Integrins αVβ3 RGD peptides SAR studies
Dulbecco's phosphate buffered saline
Minimum essential medium
The authors thank Carmela Michalek and Marco Wißbrock for skillful technical assistance. Financial support came from the NRW Graduate School in Bioinformatics and Genome Research, Bielefeld University (PhD Fellowship to K.G.), the EU (Marie Curie Fellowship to S.R.G.), and Deutsche Forschungsgemeinschaft, which is gratefully acknowledged.
Conflict of interest
The authors declare that they have no conflict of interest.
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