PUBLICATION

Characterization, bioactivity and pharmacokinetic study of a novel carbohydrate-peptide polymer: Glycol-split heparin-endostatin2 (GSHP-ES2)

Authors
Sun, F., Wang, Z., Yang, Z., Li, Y., Cui, H., Liu, C., Gao, D., Wang, F., Tan, H.
ID
ZDB-PUB-190103-1
Date
2019
Source
Carbohydrate Polymers   207: 79-90 (Journal)
Registered Authors
Keywords
Anti-angiogenesis, ES2, Glycol-split heparin, Stability, Zebra fish
MeSH Terms
  • Angiogenesis Inhibitors/chemical synthesis
  • Angiogenesis Inhibitors/pharmacokinetics
  • Angiogenesis Inhibitors/pharmacology*
  • Angiogenesis Inhibitors/toxicity
  • Animals
  • Cell Line
  • Cell Movement/drug effects
  • Chickens
  • Drug Stability
  • Endostatins/chemical synthesis
  • Endostatins/pharmacokinetics
  • Endostatins/pharmacology*
  • Endostatins/toxicity
  • Female
  • Glycopeptides/chemical synthesis
  • Glycopeptides/pharmacokinetics
  • Glycopeptides/pharmacology*
  • Glycopeptides/toxicity
  • Half-Life
  • Heparin/chemistry*
  • Humans
  • Mice, Inbred BALB C
  • Oligopeptides/chemical synthesis
  • Oligopeptides/pharmacokinetics
  • Oligopeptides/pharmacology*
  • Oligopeptides/toxicity
  • Zebrafish
PubMed
30600066 Full text @ Carbohydr. Polym.
Abstract
Endostatin (ES) has attracted considerable attention for the treatment of anti-angiogenesis-related disorders. An 11-amino-acid peptide (ES2, IVRRADRAAVP) from the amino terminal of ES is of interest because it is the main active fragment of ES. However, both ES and ES2 have a poor stability and a short half-life, and other disadvantages need to be further resolved. Thus, we conjugated ES2 to glycol-split heparin derivatives (GSHPs) to yield the polymer-peptide conjugate, GSHP-ES2. This study showed that GSHP-ES2 exhibited increased stability, a wider pH activity range, better inhibition of endothelial cell proliferation, migration and tube formation in vitro, better anti-angiogenic activity and a longer half-life in vivo compared with ES2. These results also indicate that GSHP-ES2 has good potential for the treatment of angiogenesis-related diseases, either alone or in combination with other chemicals.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping