Arg-Gly-Asp (RGD) Peptides - NEWLY UPDATED!
Integrins are heterodimeric cell surface receptors that were found in early studies to mediate adhesion between cells and the extracellular matrix (ECM), by binding to ligands with an exposed arginine-glycine-aspartate (RGD) sequence. These receptors also stimulate intracellular signaling and gene expression involved in cell growth, migration, and survival. These same processes, if not properly regulated, can lead to thrombosis, inflammation, and cancer. In fact, integrins have been demonstrated to be participants in these diseases and can also act as disease markers. Because of this, research has focused on developing RGD peptides that could mimic cell adhesion proteins and bind to integrins. The diverse applications for these peptides include inhibiting apoptosis, angiogenesis, and tumor formation, coating surfaces for use as biomaterials, enhancing drug delivery systems, and imaging for diagnostic purposes.
Peptides International offers a variety of cyclic RGD peptides and peptide HN 2 templates which confer greater stability and selectivity over linear peptides. cyclo(Arg-Gly-Asp-D-Phe-Lys) (PCI-3661-PI) can be functionalized with various linker molecules through the amino group on the lysine residue. These linkers can act as spacers or anchors for diverse surfaces. For example, linkage of this peptide with an acrylamide group allowed attachment to poly(methyl methacrylate) surfaces and led to improved binding to osteoblast cells and increased circulation time in the body. Others have functionalized this peptide with polyethylene glycol for enhanced binding to lysosomes for targeted drug delivery, resulting in effective tumor regression. Alanine replacement of glycine yields a negative control variant for this cyclic peptide, cyclo(Arg-Ala-Asp-D-Phe-Lys). Functionalized versions of cyclo(RGDfK) such as cyclo[Arg-Gly-Asp-D-Phe-Lys(PEG-PEG)] are also available.
This analog contains two mini-PEG derivatives (FXX- 5521-PI) or 8-amino-3,6-dioxaoctanoic acids that act as spacers between ligand and lipid head groups, to allow for more efficient binding to lipid surfaces. [Arg-Gly-Asp-D-Phe-Lys(Biotin-PEG-PEG)] (PCI-3697- PI) analog contains 2 PEG spacers and is biotinylated for use as a reporting tag. Previous studies have used biotinylated peptides for histological staining of RGD peptides in tissue sections. The cyclo[Arg-Gly-Asp-D- Phe-Lys(Ac-SCH2CO)] (PCI-3699-PI) analog contains an S-acetylthioacetyl group, which following deprotection, can allow coupling to liposomes via a thioether bond.
A bicyclic RGD peptide, H-Glu[cyclo(Arg-Gly-Asp-D-Phe-Lys)]2, was recently reported to possess high affinity for αvβ3 integrin. Conjugation of E-[c(RGDfK)2] with a DOTA chelator allowed for radiolabeling, and this radiolabeled peptide was demonstrated to significantly delay tumor growth in mice and have high, specific tumor uptake in human cancer xenograft, suggesting a possible role in imaging as well as potential therapy. In addition, cyclo(Arg-Gly-Asp-D-Phe-Glu) and cyclo(Arg-Gly-Asp-D-Tyr-Lys) are also available for potential imaging. The latter can be radiolabeled through the tyrosine residue or a linker, which can be attached via the side chain amino group of lysine.0 A bicyclic form of this peptide, H-E[c(RGDyK)]2 (PCI-3899-PI), has been recently modified with labels via the glutamine residue, allowing for enhanced imaging and tumor targeting.
RGD peptides are proving to be promising new tools for drug therapy and imaging of tumors, thrombosis, and inflammatory-related diseases. Peptides International provides the proper tools for further exploration and manipulation of this intriguing group of peptides for research applications.
Authors from Peptides International
Target: Cancer. Mission: Search & Destroy.Continuing the recent research focus on cancer, here is a comprehensive accounting of oncology tools.
Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of αVβ3 Integrin ActivitySci Rep., 7, 3185 (2017).
Tuning Into Peptide-Based Radiopharmaceuticals ResearchDr. Andrzej (Dr. RGD) Czerwinski gives an overview of recent developments in peptide-based radiopharmaceuticals. The post includes insights from one of the cited authors as well.
Dr. RGD Gives ReferencesWherein Dr. Czerwinski submits some references to elucidate points Dr. Pennington was making in a blog post a few of weeks ago...
99mTc-Galacto-RGD2: A Novel 99mTc-Labeled Cyclic RGD Peptide Dimer Useful for Tumor ImagingMol. Pharmaceutics 2013 Oct (9), pp 3304–3314 doi: 10.1021/mp400085d.