Molecular Design of Bioconjugated Cell Adhesion Peptide with a Water-Soluble Polymeric Modifier for Enhancement of Antimetastatic Effect

Authors: Yamamoto Y.; Tsutsumi Y.; Mayumi T.

Source: Current Drug Targets, Volume 3, Number 2, April 2002 , pp. 123-130(8)

Publisher: Bentham Science Publishers

Abstract:

The adhesive interaction of tumor cells with various components of the extracellular matrix (ECM), such as laminin and fibronectin appears to play a crucial role in tumor metastasis. It has been reported that adhesive peptides, such as Tyr-Ile-Gly-Ser-Arg (YIGSR) in laminin and Arg-Gly-Asp (RGD), inhibited adhesion and invasion of various tumor cells to ECM in vitro, and exhibited inhibitory effects on pulmonary metastasis of B16-BL6 melanoma cells in mice. However, large doses of these peptides were required for significant anti-metastatic effects in vivo, probably due to their rapid degradation by various peptidases and their rapid excretion from the blood into the urine. To overcome these problems, the development of an appropriate drug delivery system (DDS) is required to improve in vivo stability and prolong plasma half-lives. Several strategies such as peptide-cyclization and D-amino acid substation have been reported to improve stability in blood by inhibiting enzymatic degradation. However, even these approaches have proven insufficient to overcome rapid renal clearance from the circulation. On the other hand, bioconjugation with water-soluble polymeric modifiers could markedly prolong the plasma half-lives by not only increasing peptidase resistance but also impeding renal excretion. In addition, it is possible to strictly control the in vivo pharmacokinetics of a peptide by introducing functional molecules with targeting or slow release capacities to the polymeric modifier. In this review we demonstrate with reference to our recent studies that bioconjugation of adhesive peptides with the appropriate polymeric modifier can enhance antimetastatic activity and may facilitate therapeutic use.

Keywords: Polymeric modifier; Pulmonary metastasis; pegylation; Bioactive proteins; bioconjugation; proteins

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389450024605427

Publication date: 2002-04-01

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

• In this: publication
• By this: publisher
• In this Subject: Pharmacology
• By this author: Yamamoto Y. ;  Tsutsumi Y. ;  Mayumi T.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers