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Updated: May 14, 2026

Micropatterned Surfaces to Study Hyaluronic Acid Interactions with Cancer Cells
Published on: December 22, 2010
Conjugation of hyaluronan to proteins
Anna Mero1, Matteo Pasqualin, Monica Campisi
1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padua, Italy.
Abstract:
Polymer conjugation has been widely exploited to prolong half-life and reduce immunogenicity of therapeutic proteins. Here, the potentials of hyaluronic acid (HA) have been investigated by studying the conjugates with two model enzymes, trypsin and RNase A, and with insulin. As the direct coupling of proteins to the HA's carboxylic groups can cause cross-linking problems, a hyaluronan-aldehyde derivative has been synthesized for N-terminal site-selective conjugation. HA conjugation, termed HAylation, preserved the activities of enzymes and their thermal stabilities. Insulin HAylation was studied by preparing two conjugates with different peptide loadings (32% and 17%, w/w). Noticeably, the conjugate with the lower loading showed the greater effect on blood glucose level. The 17% HA-insulin conjugate showed a lowering effect on blood glucose level for up to 6h, while free insulin exhausted its action after 1h. This study highlights the potentials of hyaluronan-aldehyde for protein delivery.
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