Synthetic RGD-containing alpha-helical coiled coil peptides promote integrin-dependent cell adhesion.
Details
Serval ID
serval:BIB_6D785D120087
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Synthetic RGD-containing alpha-helical coiled coil peptides promote integrin-dependent cell adhesion.
Journal
Journal of Peptide Science
ISSN
1075-2617
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
12
Number
3
Pages
206-212
Language
english
Notes
Publication types: Journal Article
Abstract
Integrin receptors are the main mediators of cell adhesion to the extracellular matrix. They bind to their ligands by interacting with short amino acid sequences, such as the RGD sequence. Soluble, small RGD-based peptides have been used to block integrin-binding to ligands, thereby interfering with cell adhesion, migration and survival, while substrate-immobilized RGD sequences have been used to enhance cell binding to artificial surfaces. This approach has several important medical applications, e.g. in suppression of tumor angiogenesis or stimulation of bone formation around implants. However, the relatively weak affinity of short RGD-containing peptides often results in incomplete integrin inhibition or ineffective ligation. In this work, we designed and synthesized several new multivalent RGD-containing molecules and tested their ability to inhibit or to promote integrin-dependent cell adhesion when used in solution or immobilized on substrates, respectively. These molecules consist of an oligomeric structure formed by alpha-helical coiled coil peptides fused at their amino-terminal ends with an RGD-containing fragment. When immobilized on a substrate, these peptides specifically promoted integrin alphaVbeta3-dependent cell adhesion, but when used in solution, they blocked alphaVbeta3-dependent cell adhesion to the natural substrates fibronectin and vitronectin. One of the peptides was nearly 10-fold more efficient than fibronectin or vitronectin in promoting cell adhesion, and almost 100-fold more efficient than a linear RGD tripeptide in blocking adhesion. These results indicate that alpha-helical coiled coil peptides carrying an amino-terminal RGD motif can be used as soluble antagonists or surface-immobilized agonists to efficiently inhibit or promote integrin alphaVbeta3-mediated cell adhesion, respectively.
Keywords
Cell Adhesion/drug effects, Cell Adhesion/physiology, Cell Line, Tumor, Humans, Integrin alphaVbeta3/chemistry, Integrin alphaVbeta3/drug effects, Ligands, Oligopeptides/chemical synthesis, Oligopeptides/chemistry, Protein Structure, Secondary/physiology, Protein Structure, Tertiary/physiology, Structure-Activity Relationship
Pubmed
Web of science
Create date
24/01/2008 15:55
Last modification date
20/08/2019 15:27