Main receptors for Collagen Ligands Collection
Most scientists who examine collagen-binding proteins would like to go inside the collagen and make more profound studies on collagen active sites.
What stops them are the limitations imposed by the complex collagen structure and the material available to the research community.
That is why we created the Collagen Ligands Collection (CLC).
Glycoprotein VI:
An immune receptor expressed on the platelet surface, GPVI is the key receptor that binds exposed collagen in the vessel wall and activates platelets.
GPVI is a useful therapeutic target in thrombotic disease, and our GPVI ligands contribute to research in this area.
GPVI-binding products:
We offer several Collagen-Related Peptides, triple-helical peptides that bind to GPVI, for use in research and diagnostic applications.
mCRP - Monomeric CRP. GCO-(GPO)10-GCOG-NH2.
The active sequence of our CRPs is OGPOGP, which docks onto D1 of GPVI. The Cysteine residues can be used for crosslinking, or to derivatise the peptide.
mCRP can be used in platelet binding assays, and for coating of surfaces for shear flow experimentation.
It will coat onto glass surfaces for microscopic analysis or plastic surfaces for binding assays.
No use for aggregometry or flow cytometry.
CRP-XL - Crosslinked CRP.
A potent activator of platelets, as a consequence of chemical crosslinking using the free cysteine residues and N-terminal amino groups.
The polymerisation so introduced allows CRP-XL to bind and cluster GPVI on the platelet surface, a process that is a prerequisite for platelet activation.
CRP-XL is used worldwide in haemostasis research, finding application in aggregometry and flow cytometry.
CRP-QZ - A novel GPVI ligand. A GPO polymer.
CRP-QZ is also a potent activator of platelets through GPVI. No crosslinking step is involved in its production, and it is more stable on storage.
Useful in aggregometry, flow cytometry and other platelet applications.
Discoidin Domain Receptors:
Widely and differentially expressed receptor tyrosine kinases (RTKs), linked to several pathologies including inflammation, fibrosis, arthritis and cancer.
The only RTKs known to bind collagen, recognising the conserved site in collagens I, II and III, and receptor-specific sites in collagen IV (DDR1) and collagen X (DDR2).
Selectivity of DDR-binding peptides:
Similar considerations apply to binding of DDR1 and DDR2: the same collagen residues are involved (Xu, Mat Biol 2011).
Triple Helical Peptides supplies several DDR-binding peptides:
1. [Gxx’] = GPRGQOGVNleGFO (recommended). Source of the sequence: Collagen III.
2. [Gxx’] = GPRGQOGVMGFO. Source of the sequence: Collagen III.
3. [Gxx’] = GARGQOGVMGFO. Source of the sequence: Collagen II.
4. [Gxx’] = GVMGFO. Source of the sequence: Collagen II and III.
Availability:
The above peptides are available in standard format, i.e., as
GPC-[GPP]5-[Gxx’]n-[GPP]5-GPC-NH2 from stock.
Derivatised peptides (biotinylated or with fluorophores) or other formats (shorter forms for structural studies) – please enquire.
OSCAR – Osteoclast-Associated Receptor:
Expressed on the monocyte lineage, OSCAR is a co-receptor for the differentiation of monocytes into osteoclasts.
OSCAR is an immune receptor with two Ig-like domains, showing homology with GPVI. Each domain can bind collagen,
and it seems likely that receptor clustering is important in monocyte osteoclast progression.
Diversity of OSCAR-binding motifs:
Several conserved loci in Collagens I, II and III contain OSCAR binding motifs.
Triple Helical Peptides supplies several OSCAR-binding peptides:
1. [Gxx’] = GAOGPQGFQ, and GP[A/O]G[P/S][O/S]GFQ. Source of the sequence: Collagen I and II.
2. [Gxx’] = GPOGPAGF[A/O]. Source of the sequence: Collagen I, II, and III.
3. [Gxx’] = GASGDR. Source of the sequence: Collagen II.
Availability:
The above peptides are available in standard format, i.e., as
GPC-[GPP]5-[Gxx’]n-[GPP]5-GPC-NH2 from stock.
Derivatised peptides (biotinylated or with fluorophores) or other formats (shorter forms for structural studies) – please enquire.
Collagen-binding Integrins:
α1β1, α2β1, α10β1 and α11β1 are widely-expressed heterodimeric adhesion receptors, where the α-subunit I-domain contains the ligand binding site.
Expression varies with cell type and state of differentiation. We can provide peptides recognising each integrin which contain a 6-residue guest sequence (such as GFOGER)
within GPC-[GPP]5- and -[GPP]5-GPC-NH2 hosts. The sequence GFOGER was the first such motif to be discovered, in a CB peptide of α1(I),
and occurs in a conserved locus in Collagen II, and in Collagen IV. Our peptides are used for coating surfaces or modifying scaffolds to support cell attachment, for example.
Selectivity of integrin-binding peptides:
Peptides containing the GFOGER motif bind with high affinity to each of the collagen-binding integrins.
Other motifs with the same generic sequence occur elsewhere in the collagens. GLOGEN (collagen III) has greater affinity for α1β1 and α10β1 than GFOGER,
whilst GROGER (collagens I and III) does not bind α10β1 but is a good ligand for the other three integrins. GVOGEA (collagen II) is a moderate ligand for both α1β1 and α10β1
but not the other two. Several lower affinity motifs exist, such as GMOGER and GAOGER. When expressed on a cell, affinity of these integrins can be increased by cell activation.
Triple Helical Peptides supplies several Integrin-binding peptides:
1. For α1β1: [Gxx’] can be one of the following: GLOGEN > GFOGER = GLOGER = GROGER > GVOGEA.
2. For α2β1: [Gxx’] can be one of the following: GFOGER > GLOGER ≥ GROGER ≥ GLOGEN.
3. For α10β1: [Gxx’] can be one of the following: GLOGEN > GFOGER = GLOGER > GVOGEA, but not GROGER.
4. For α11β1: [Gxx’] can be one of the following: GFOGER > GLOGER ≥ GROGER ≥ GLOGEN.
Availability:
The above peptides are available in standard format, i.e., as
GPC-[GPP]5-[Gxx’]n-[GPP]5-GPC-NH2 from stock.
Derivatised peptides (biotinylated or with fluorophores) or other formats (shorter forms for structural studies) – please enquire.
Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1)
LAIR1 is an immune receptor expressed on a range of immune cells, including NK and T and B cells, where it exerts an inhibitory function on immune responses.
Its single Ig-fold extracellular domain binds collagen (and C1q, Lung Surfactant Protein D and adiponectin, which are also triple-helical molecules).
Leukocyte-associated immunoglobulin-like receptor-2 (LAIR-2)
LAIR2, a distinct gene product, is a soluble homologue of LAIR1, which, by competing with its binding sites on collagen, may modulate the action of LAIR1.
LAIR-binding products:
Like GPVI, LAIR1 binds GPO-rich tracts of collagen, and there is some overlap in binding properties between these immune receptors.
Several CLC peptides are good ligands for the LAIRs, whilst mCRP has lower apparent affinity than them.
Triple Helical Peptides supplies several LAIR-binding peptides:
1. CLC II-30.
2. CLC II-56.
3. CLC III-1.
4. CLC III-30.
5. CLC III-38.
6. CLC III-51.
LAIR2 appears more promiscuous, binding a larger repertoire of CLC peptides including all those above, and has a higher relative affinity for mCRP than LAIR1.
Availability:
The above peptides are available in standard format, i.e., as
GPC-[GPP]5-[Gxx’]-[GPP]5-GPC-NH2 from stock.
Derivatised peptides (biotinylated or with fluorophores) or other formats (shorter forms for structural studies) – please enquire.