Dataset Information

TargetAntiAngio: A Sequence-Based Tool for the Prediction and Analysis of Anti-Angiogenic Peptides.

ABSTRACT: Cancer remains one of the major causes of death worldwide. Angiogenesis is crucial for the pathogenesis of various human diseases, especially solid tumors. The discovery of anti-angiogenic peptides is a promising therapeutic route for cancer treatment. Thus, reliably identifying anti-angiogenic peptides is extremely important for understanding their biophysical and biochemical properties that serve as the basis for the discovery of new anti-cancer drugs. This study aims to develop an efficient and interpretable computational model called TargetAntiAngio for predicting and characterizing anti-angiogenic peptides. TargetAntiAngio was developed using the random forest classifier in conjunction with various classes of peptide features. It was observed via an independent validation test that TargetAntiAngio can identify anti-angiogenic peptides with an average accuracy of 77.50% on an objective benchmark dataset. Comparisons demonstrated that TargetAntiAngio is superior to other existing methods. In addition, results revealed the following important characteristics of anti-angiogenic peptides: (i) disulfide bond forming Cys residues play an important role for inhibiting blood vessel proliferation; (ii) Cys located at the C-terminal domain can decrease endothelial formatting activity and suppress tumor growth; and (iii) Cyclic disulfide-rich peptides contribute to the inhibition of angiogenesis and cell migration, selectivity and stability. Finally, for the convenience of experimental scientists, the TargetAntiAngio web server was established and made freely available online.

SUBMITTER: Laengsri V

PROVIDER: S-EPMC6628072 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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TargetAntiAngio: A Sequence-Based Tool for the Prediction and Analysis of Anti-Angiogenic Peptides.

Laengsri Vishuda V Nantasenamat Chanin C Schaduangrat Nalini N Nuchnoi Pornlada P Prachayasittikul Virapong V Shoombuatong Watshara W

International journal of molecular sciences 20190617 12

Cancer remains one of the major causes of death worldwide. Angiogenesis is crucial for the pathogenesis of various human diseases, especially solid tumors. The discovery of anti-angiogenic peptides is a promising therapeutic route for cancer treatment. Thus, reliably identifying anti-angiogenic peptides is extremely important for understanding their biophysical and biochemical properties that serve as the basis for the discovery of new anti-cancer drugs. This study aims to develop an efficient a ...[more]

PMID: 31212918

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Project description:Abnormal migration and proliferation of endothelial cells (EC) drive neovascular retinopathies. While anti-VEGF treatment slows progression, pathology is often supported by decrease in intraocular pigment epithelium-derived factor (PEDF), an endogenous inhibitor of angiogenesis. A surface helical 34-mer peptide of PEDF, comprising this activity, is efficacious in animal models of neovascular retina disease but remains impractically large for therapeutic use. We sought smaller fragments within this sequence that mitigate choroidal neovascularization (CNV). Expecting rapid intravitreal (IVT) clearance, we also developed a method to reversibly attach peptides to nano-carriers for extended delivery. Synthetic fragments of 34-mer yielded smaller anti-angiogenic peptides, and N-terminal capping with dicarboxylic acids did not diminish activity. Charge restoration via substitution of an internal aspartate by asparagine improved potency, achieving low nM apoptotic response in VEGF-activated EC. Two optimized peptides (PEDF 335, 8-mer and PEDF 336, 9-mer) were tested in a mouse model of laser-induced CNV. IVT injection of either peptide, 2-5 days before laser treatment, gave significant CNV decrease at day +14 post laser treatment. The 8-mer also decreased CNV, when administered as eye drops. Also examined was a nanoparticle-conjugate (NPC) prodrug of the 9-mer, having positive zeta potential, expected to display longer intraocular residence. This NPC showed extended efficacy, even when injected 14 days before laser treatment. Neither inflammatory cells nor other histopathologic abnormalities were seen in rabbit eyes harvested 14 days following IVT injection of PEDF 336 (>200 ?g). No rabbit or mouse eye irritation was observed over 12-17 days of PEDF 335 eye drops (10 mM). Viability was unaffected in 3 retinal and 2 choroidal cell types by PEDF 335 up to 100 ?M, PEDF 336 (100 ?M) gave slight growth inhibition only in choroidal EC. A small anti-angiogenic PEDF epitope (G-Y-D-L-Y-R-V) was identified, variants (adipic-Sar-Y-N-L-Y-R-V) mitigate CNV, with clinical potential in treating neovascular retinopathy. Their shared active motif, Y - - - R, is found in laminin (Ln) peptide YIGSR, which binds Ln receptor 67LR, a known high-affinity ligand of PEDF 34-mer.

Dataset Information

TargetAntiAngio: A Sequence-Based Tool for the Prediction and Analysis of Anti-Angiogenic Peptides.

Publications

TargetAntiAngio: A Sequence-Based Tool for the Prediction and Analysis of Anti-Angiogenic Peptides.

Similar Datasets

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