3S1K

The Development of Peptide-based Tools for the Analysis of Angiogenesis

Summary for 3S1K

• Entry DOI: 10.2210/pdb3s1k/pdb
• Related: 3S1B
• Descriptor: Z-domain, Vascular endothelial growth factor A (3 entities in total)
• Functional Keywords: vegf, cystine knot, z-domain, phage-display, cystine-knot, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P15692
• Total number of polymer chains: 4
• Total formula weight: 37242.29

Authors

Murray, J.M.,Wiesmann, C. (deposition date: 2011-05-15, release date: 2011-08-17, Last modification date: 2024-10-30)

Primary citation

Fedorova, A.,Zobel, K.,Gill, H.S.,Ogasawara, A.,Flores, J.E.,Tinianow, J.N.,Vanderbilt, A.N.,Wu, P.,Meng, Y.G.,Williams, S.P.,Wiesmann, C.,Murray, J.,Marik, J.,Deshayes, K.
The development of Peptide-based tools for the analysis of angiogenesis.
Chem.Biol., 18:839-845, 2011

PubMed Abstract: Limitations to the application of molecularly targeted cancer therapies are the inability to accurately match patient with effective treatment and the absence of a prompt readout of posttreatment response. Noninvasive agents that rapidly report vascular endothelial growth factor (VEGF) levels using positron emission tomography (PET) have the potential to enhance anti-angiogenesis therapies. Using phage display, two distinct classes of peptides were identified that bind to VEGF with nanomolar affinity and high selectivity. Co-crystal structures of these different peptide classes demonstrate that both bind to the receptor-binding region of VEGF. (18)F-radiolabelling of these peptides facilitated the acquisition of PET images of tumor VEGF levels in a HM7 xenograph model. The images obtained from one 59-residue probe, (18)F-Z-3B, 2 hr postinjection are comparable to those obtained with anti-VEGF antibody B20 72 hr postinjection. Furthermore, VEGF levels in growing SKOV3 tumors were followed using (18)F-Z-3B as a PET probe with VEGF levels increasing with tumor size.

PubMed: 21802005
DOI: 10.1016/j.chembiol.2011.05.011

Experimental method

X-RAY DIFFRACTION (2.55 Å)