Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Shi, Li Feng; Wu, Yan; Li, Cai Yun

doi:10.3802/jgo.2015.26.4.327

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…A typical feature of antibodies is their slow drug metabolism, unlike small pharmaceutical molecules and peptides in vivo. Shi and colleagues screened peptide III (WHWLPNLRHYAS) targeting the extracellular fragment of recombinant human VEGFR-3/ Flt-4 through a phage-displayed random peptide library (34), but the efficacy of VEGFR-3 imaging was lower than that of 68 Ga-DOTA-TMVP1. Representative torso maximum intensity projection images.…”

Section: Discussionmentioning

confidence: 99%

Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer

Zhang

Cai

et al. 2020

Clinical Cancer Research

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Tumor periphery and lymph nodes of tumorinduced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel 68 Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer.Experimental Design: The DOTA-conjugated TMVP1 peptide was labeled with radionuclide 68 Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of 68 Ga-DOTA-TMVP1 in vivo. In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with 68 Ga-DOTA-TMVP1.Results: DOTA-TMVP1 was successfully labeled with 68 Ga. LECs showed higher binding capacity with 68 Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of 68 Ga-DOTA-TMVP1 was comparable with that of 18 F-FDG PET/CT.Conclusions: 68 Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer

Zhang

Cai

et al. 2020

Clinical Cancer Research

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“…Several peptide sequences binding FLT4 were previously identified using phage display. [ 33 ] The highest affinity peptide sequence, WHWLPNLRHYAS, was selected as a targeting moiety and attached to a palmitoleic acid tail via a PEG spacer (Figure 1D). We have previously used constructs of this format with polymersomes for optimization of cell‐selective targeting.…”

Section: Figurementioning

confidence: 99%

Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma

Stack

Vincent

Vahabikashi

et al. 2020

Small

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Increased stiffness of the Schlemm's canal (SC) endothelium in the aqueous humor outflow pathways has been associated with elevated intraocular pressure (IOP) in glaucoma. Novel treatments that relax this endothelium, such as actin depolymerizers and rho kinase inhibitors, are in development. Unfortunately, these treatments have undesirable off‐target effects and a lower than desired potency. To address these issues, a targeted PEG‐b‐PPS micelle loaded with actin depolymerizer latrunculin A (tLatA‐MC) is developed. Targeting of SC cells is achieved by modifying the micelle surface with a high affinity peptide that binds the VEGFR3/FLT4 receptor, a lymphatic lineage marker found to be highly expressed by SC cells relative to other ocular cells. During in vitro optimization, increasing the peptide surface density increased micellar uptake in SC cells while unexpectedly decreasing uptake by human umbilical vein endothelial cells (HUVEC). The functional efficacy of tLatA‐MC, as measured by decreased SC cell stiffness compared to non‐targeted micelles (ntLatA‐MC) or targeted blank micelles (tBL‐MC), is verified using atomic force microscopy. tLatA‐MC reduced IOP in an in vivo mouse model by 30–50%. The results validate the use of a cell‐softening nanotherapy to selectively modulate stiffness of SC cells for therapeutic reduction of IOP and treatment of glaucoma.

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“…The screening of peptides binding to EtMIC3-bc1 protein was carried out as described in previous reports [ 14 , 17 ] with some modifications based on phage display peptide library kit (New England Biolabs, USA). Briefly, 96-well plates were coated with 100 μL per well of purified EtMIC3-bc1 protein (100 μg/mL), and incubated overnight at 4 ℃.…”

Section: Methodsmentioning

confidence: 99%

Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells

Chen

et al. 2021

Vet Res

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Avian coccidiosis caused by Eimeria leads to huge economic losses on the global poultry industry. In this study, microneme adhesive repeat regions (MARR) bc1 of E. tenella microneme protein 3 (EtMIC3-bc1) was used as ligand, and peptides binding to EtMIC3 were screened from a phage display peptide library. The positive phage clones were checked by enzyme-linked immunosorbent assay (ELISA). Competitive ELISA was applied to further verify the binding capability between the positive phages and recombinant EtMIC3-bc1 protein or sporozoites protein. The inhibitory effects of target peptides on sporozoites invasion of MDBK cells were measured in vitro. Chickens were orally administrated with target positive phages and the protective effects against homologous challenge were evaluated. The model of three-dimensional (3D) structure for EtMIC3-bc1 was conducted, and molecular docking between target peptides and EtMIC3-bc1 model was analyzed. The results demonstrated that three selected positive phages specifically bind to EtMIC3-bc1 protein. The three peptides A, D and W effectively inhibited invasion of MDBK cells by sporozoites, showing inhibited ratio of 71.8%, 54.6% and 20.8%, respectively. Chickens in the group orally inoculated with phages A displayed more protective efficacies against homologous challenge than other groups. Molecular docking showed that amino acids in three peptides, especially in peptide A, insert into the hydrophobic groove of EtMIC3-bc1 protein, and bind to EtMIC3-bc1 through intermolecular hydrogen bonds. Taken together, the results suggest EtMIC3-binding peptides inhibit sporozoites entry into host cells. This study provides new idea for exploring novel strategies against coccidiosis.

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Identification of high-affinity VEGFR3-binding peptides through a phage-displayed random peptide library

Cited by 10 publications

References 35 publications

Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer

Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer

Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma

Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells

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