Design, synthesis, and activity evaluation of a new 5-fluorouracil prodrug containing an Asn-Gly-Arg(NO2)COOCH3 tripeptide.

Abstract

Aminopeptidase N (APN/CD13) of the M1 family is a broad specificity enzyme that is intimately involved in tumor angiogenesis and metastasis. Asparagine-glycine-arginine (NGR) is a tumor-homing tripeptide, which can selectively combine with APN/CD13 that is overexpressed on the surface of some tumor cells. Various anti-tumor drugs can be conjugated to NGR to improve selectivity, efficacy, and to decrease drug toxicity. In this study, a tripeptide NGR(NO2) was synthesized and conjugated with 5-fluorouracil. The anti-tumor activities of this new prodrug were evaluated in vivo. More significant anti-tumor effects were observed over the parent 5-fluorouracil.

• Authors: Yepeng Luan, Fanbo Jing, Jian Zhang, Mingming Zou, Xuejian Wang, Yuping Jia, Ning Liu, Jiajia Mou, Wenfang Xu
• Journal: Protein and peptide letters (Protein Pept Lett) Vol. 19 Issue 10 Pg. 1122-31 (Oct 2012) ISSN: 1875-5305 [Electronic] Netherlands
• PMID: 22512656 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 13F-1 compound
• Antimetabolites, Antineoplastic
• Drug Combinations
• Laminin
• NGR peptide
• Oligopeptides
• Prodrugs
• Proteoglycans
• matrigel
• Collagen
• CD13 Antigens
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• CD13 Antigens (chemistry, metabolism)
• Cell Movement (drug effects)
• Cells, Cultured
• Collagen (metabolism)
• Drug Combinations
• Drug Design
• Female
• Fluorouracil (analogs & derivatives, chemistry, pharmacology)
• Human Umbilical Vein Endothelial Cells (cytology, drug effects)
• Humans
• Laminin (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis
• Neovascularization, Pathologic (prevention & control)
• Oligopeptides (chemistry, metabolism, pharmacology)
• Prodrugs (chemistry, pharmacology)
• Proteoglycans (metabolism)
• Sarcoma 180 (drug therapy, pathology)
• Xenograft Model Antitumor Assays