Integrins are a family of structurally, immunochemically, and functionally related heterodimeric cell-surface receptors mediating adhesion between cells and the extracellular matrix (ECM) by binding to ligands with an exposed arginine-glycine-aspartate (RGD) sequence. Integrins also stimulate intracellular signaling and gene expression involved in cell growth, migration, and survival. If not properly process-regulated, integrins are found to be related to diseases such as thrombosis, inflammation, and cancer. Specifically, the RGD motif is recognized by integrins α_νβ₃ and α_νβ₅ which are overexpressed in many tumors and thus have become promising diagnostic indicators and therapeutic targets.

Iris Biotech offers a variety of cyclic RGD peptides which are conformationally rigid and typically display enhanced metabolic stability over their linear counterparts.

One example possessing very high affinity for the α_vβ₃ integrin is the dimeric peptide E[c(RGDfK)]₂ (LS-3980), that consists of two cyclic pentapeptides c(RGDfK) linked by a glutamic acid residue. Thus, this dimeric RGD peptide shows high tumor targeting properties. It serves as an integrin inhibitor and gained interest in non-small-cell lung cancer treatment. It can be easily conjugated to drug molecules, chelators, or dyes. In this context, please see LS-3950 (ICG-E[c(RGDfK)]₂), the ICG conjugate of LS-3980 combining the fluorescent properties of ICG and the favorable α_vβ₃-binding capabilities of LS-3980 allowing tumor targeting.

Cyclo-[RGDfK(TPP)] (LS-3920) serves as cyclic RGD peptide for the preparation of multicellular tumor spheroids (MTS) – 3D in vitro models that mimic the in vivo tumor environment.

➔ In case you don’t find your desired derivative in our Webshop, send your inquiry to our Custom Synthesis Service!

References:

• RGD and Other Recognition Sequences for Integrins; E. Ruoslahti; Annu Rev Cell Dev Biol. 1996; 12: 697-715. https://doi.org/10.1146/annurev.cellbio.12.1.697
• Integrins: A Family of Cell Surface Receptors; R. O. Hynes; Cell 1987; 48: 549-54. https://doi.org/10.1016/0092-8674(87)90233-9
• Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals; D. Gang, D. W. Kim, H.-S. Park; Genes 2018; 9: 557. https://doi.org/10.3390/genes9110557
• Tumor targeting with radiolabeled alpha(v)beta(3) integrin binding peptides in a nude mouse model. M. L. Janssen, W. J. Oyen, I. Dijkgraaf, L. F. Massuger, C. Frielink, D. S. Edwards, M. Rajopadhye, H. Boonstra, F. H. Corstens and O. C. Boerman; Cancer Res. 2002; 62(21): 6146-6151. https://cancerres.aacrjournals.org/content/62/21/6146
• microPET imaging of glioma integrin alpha(v)beta(3) expression using (64)Cu-labeled tetrameric RGD peptide. Y. Wu, X. Zhang, Z. Xiong, Z. Cheng, D. R. Fisher, S. Liu, S. S. Gambhir and X. Chen; J. Nucl. Med. 2005; 46(10): 1707-1718. http://jnm.snmjournals.org/content/46/10/1707.full
• 3D in vitro co-culture models based on normal cells and tumor spheroids formed by cyclic RGD-peptide induced cell self-assembly; R. Akasov, A. Gileva, D. Zaytseva-Zotova, S. Burov, I. Chevalot, E. Guedon and E. Markvicheva; Biotechnol. Lett. 2017; 39: 45-53. https://doi.org/10.1007/s10529-016-2218-9
• Sialylation facilitates self-assembly of 3D multicellular prostaspheres by using cyclo-RGDfK(TPP) peptide; S. Haq, V. Samuel, F. Haxho, R. Akasov, M. Leko, S. V. Burov, E. Markvicheva and M. R. Szewczuk; OncoTargets Ther 2017; 10: 2427-2447. https://doi.org/10.2147/ott.s133563
• Sialylation transmogrifies human breast and pancreatic cancer cells into 3D multicellular tumor spheroids using cyclic RGD-peptide induced self-assembly; R. Akasov, S. Haq, F. Haxho, V. Samuel, S. V. Burov, E. Markvicheva, R. J. Neufeld and M. R. Szewczuk; Oncotarget 2016; 7: 66119-66134. https://doi.org/10.18632/oncotarget.11868
• Formation of multicellular tumor spheroids induced by cyclic RGD-peptides and use for anticancer drug testing in vitro; R. Akasov, D. Zaytseva-Zotova, S. Burov, M. Leko, M. Dontenwill, M. Chiper, T. Vandamme and E. Markvicheva; Int. J. Pharm. 2016; 506: 148-157. https://doi.org/10.1016/j.ijpharm.2016.04.005