Peptide Inhibitors of Vascular Endothelial Growth Factor A: Current Situation and Perspectives

Abstract

Vascular endothelial growth factors (VEGFs) are the family of extracellular signaling proteins involved in the processes of angiogenesis. VEGFA overexpression and altered regulation of VEGFA signaling pathways lead to pathological angiogenesis, which contributes to the progression of various diseases, such as age-related macular degeneration and cancer. Monoclonal antibodies and decoy receptors have been extensively used in the anti-angiogenic therapies for the neutralization of VEGFA. However, multiple side effects, solubility and aggregation issues, and the involvement of compensatory VEGFA-independent pro-angiogenic mechanisms limit the use of the existing VEGFA inhibitors. Short chemically synthesized VEGFA binding peptides are a promising alternative to these full-length proteins. In this review, we summarize anti-VEGFA peptides identified so far and discuss the molecular basis of their inhibitory activity to highlight their pharmacological potential as anti-angiogenic drugs.

Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology

“…Additionally, inhibition of SRC expression down-regulates the signaling cascade associated with tumorigenesis and progression, thereby exerting anti-cancer effects [ 71 , 72 ]. Angiogenesis is critical for tumor growth and metastasis, and angiogenesis is dependent on VEGFA [ 73 ]。…”

Structure-Based Design of Peptides Targeting VEGF/VEGFRs

“…Several peptides targeting VEGF have been reported [ 73 ], but the structure-based design of VEGF peptide binders mimicking the VEGFR binding interface has been scarcely described so far, probably reflecting a difficult surface to be addressed by rational design methods. The VEGF-A binding epitopes of VEGFR-2 involve residues spreading over Ig-like domains 2 and 3 ( Figure 2 ); they are mainly distributed around the region connecting the two receptor domains.…”

Dimer Peptide Ligands of Vascular Endothelial Growth Factor: Optimizing Linker Length for High Affinity and Antiangiogenic Activity

“…We describe here a dimerization strategy to maintain high binding affinity to VEGF through an avidity effect while keeping the size of the peptide-based ligand small. Several peptides have been described as ligands of VEGF. , The 19-amino acid VEGF binding peptide v114 was identified by phage display, and improvements of its structure have since been achieved. − We shortened this peptide to 15 amino acids and introduced a helix-stabilizing lactam bridge . The resulting peptide has an affinity of 38 nM for VEGF and has a molecular weight of 2 kDa.…”

“…Several peptides have been described as ligands of VEGF. 12,13 The 19-amino acid VEGF binding peptide v114 was identified by phage display, 14 and improvements of its structure have since been achieved. 15−17 We shortened this peptide to 15 amino acids 18 and introduced a helix-stabilizing lactam bridge.…”