Synthesis and bioactivity of a conjugate composed of green tea catechins and hyaluronic acid

Lee, Fan; Lim, Jaehong; Reithofer, Michael R.; Lee, Su Seong; Chung, Joo Eun; Hauser, Charlotte A. E.; Kurisawa, Motoichi

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol that has several biological activities, including anti-cancer activity and anti-inflammation. Hyaluronic acid (HA) is a naturally-occurring polysaccharide that is widely used as a biomaterial for drug delivery and tissue engineering due to its viscoelastic, biocompatible and biodegradable properties. By conjugating HA with EGCG, the resulting HA-EGCG conjugate is expected to exhibit not only the inherent properties of HA but also the bioactivities of EGCG. Toward this end, we report the synthesis of an amine-functionalized EGCG as an intermediate compound for conjugation to HA. EGCG was reacted with 2,2-diethoxyethylamine (DA) under acidic conditions, forming ethylamine-bridged EGCG dimers. The EGCG dimers were composed of four isomers, which were characterized by HPLC, high-resolution mass spectrometry and NMR spectroscopy. The amine-functionalized EGCG dimers were conjugated to hyaluronic acid (HA) through the formation of amide bonds. HA-EGCG conjugates demonstrated several bioactivities which were not present in unmodified HA, including resistance to hyaluronidase-mediated degradation, inhibition of cell growth and scavenging of radicals. The potential applications of HA-EGCG conjugates are discussed.

Citation

Lee, F., Lim, J., Reithofer, M. R., Lee, S. S., Chung, J. E., Hauser, C. A. E., & Kurisawa, M. (2015). Synthesis and bioactivity of a conjugate composed of green tea catechins and hyaluronic acid. Polymer chemistry, 6(24), 4462-4472. https://doi.org/10.1039/c5py00495k

• Journal Article Type: Article
• Acceptance Date: May 8, 2015
• Online Publication Date: May 11, 2015
• Publication Date: Jun 28, 2015
• Deposit Date: Jun 11, 2015
• Publicly Available Date: Jun 11, 2015
• Journal: Journal of polymer science. Part A, Polymer chemistry
• Print ISSN: 1759-9954
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 24
• Pages: 4462-4472
• DOI: https://doi.org/10.1039/c5py00495k
• Keywords: (−)-Epigallocatechin-3-gallate; Green tea catechins; Green tea polyphenols; Hyaluronic acid
• Public URL: https://hull-repository.worktribe.com/output/375121
• Publisher URL: http://pubs.rsc.org/en/content/articlelanding/2015/py/c5py00495k#!divAbstract
• Contract Date: Jun 11, 2015