PUBLICATION

Study on glyco-modification of endostatin-derived synthetic peptide endostatin2 (ES2) by soluble chitooligosaccharide

Authors
Yu, Y., Sun, F., Zhang, C., Wang, Z., Liu, J., Tan, H.
ID
ZDB-PUB-160901-4
Date
2016
Source
Carbohydrate Polymers   154: 204-13 (Journal)
Registered Authors
Keywords
Anti-angiogenic activities, Chitooligosaccharide, Endostatin-derived peptide, Glyco-modification, Heat stability
MeSH Terms
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Cell Movement/drug effects
  • Chick Embryo
  • Chitin/analogs & derivatives*
  • Chitin/chemistry
  • Chorioallantoic Membrane/blood supply
  • Chorioallantoic Membrane/drug effects
  • Drug Evaluation, Preclinical/methods
  • Embryo, Nonmammalian/drug effects
  • Endostatins/chemistry*
  • Endostatins/pharmacology*
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Peptide Fragments/chemistry*
  • Peptide Fragments/pharmacology*
  • Protein Stability
  • Solubility
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed
27577911 Full text @ Carbohydr. Polym.
Abstract
Soluble O-(2-hydroxyl)propyl-3-trimethyl ammonium chitooligosaccharide chloride (HTCOSC) was covalently conjugated to the 11-amino-acid peptide derived from amino terminus of endostatin (endostatin2, ES2, IVRRADRAAVP) to overcome its poor stability, low cell affinity and instable activity. Nuclear magnetic resonance spectroscopy and mass spectrometry was used to study the structure and molecular weight information. The anti-angiogenic activities were evaluated using cell counting Kit-8 assay, flow cytometry assay, wounding migration assay, transwell migration assay, chicken chorioallantoic membrane (CAM) assay and zebra fish angiogenesis assay. In contrast with ES2, the novel carbohydrate-polymer HTCOSC-ES2 displayed improved heat stability, higher cell affinity, better inhibition on endothelial cell proliferation, tube formation, 2-dimensional and 3-dimensional migration in vitro. According to the evaluation in CAM and zebra fish, HTCOSC-ES2 also displayed better anti-angiogenic activity than ES2 in vivo. These results indicate that HTCOSC has good properties as potential candidate for protein/peptide modifier and HTCOSC-ES2 has good potential in angiogenesis related diseases treatment.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping