Synthesis of heterotrimeric collagen peptides containing the alpha1beta1 integrin recognition site of collagen type IV.
Journal of peptide science : an official publication of the European Peptide Society
confidence
Key findings
Synthesized heterotrimeric collagen IV peptides; chain register affects triple-helix stability but minimally affects alpha1beta1 integrin binding.
View source on PubMed (PMID 12043994) ↗
- Sample size
- Not applicable
- Population
- Not applicable (synthetic chemistry / structural study)
- Dosing
- Not applicable
- Duration
- Not applicable
- Route
- Not applicable
- Blinding
- not_reported
- Controls
- none
- Drug class
- peptide
Full abstract
Collagen type IV provides a biomechanically stable scaffold into which the other constituents of basement membranes are incorporated, but it also plays an important role in cell adhesion. This occurs with collagen type IV mainly via the alpha1beta1 integrin, and the proposed epitope involved in this type of collagen/integrin interaction corresponds to a non-sequential R/Xaa/D motif, where the arginine and aspartate residues are provided by the alpha2 and alpha1 chains of the collagen molecule, respectively. Since the stagger of the three alpha chains in native collagen type IV is still unknown and different alignments of the chains lead to different spatial epitopes, two heterotrimeric collagen peptides containing the natural 457-469 sequences of the cell adhesion site were synthesized in which the single chains were assembled via disulfide bonds into the two most plausible alpha1alpha2alpha1' and alpha2alpha1alpha1' registers. The differentiated triple-helical stabilities of the two heterotrimers suggest a significant structural role of the chain register in collagen, although the binding to alpha1beta1 integrin is apparently less affected as indicated by preliminary experiments.