Chemical Modifications of Hyaluronan using DMTMM-Activated Amidation

Sammanfattning: An alternative approach to chemically modifying hyaluronan (HA) has been investigated. The triazine derivative 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) has been used to activate carboxylic groups on HA, which react further to form stable amide bonds with primary and secondary amines. The reaction can either be used to couple monoamines to HA or to produce hydrogels by using diamines that form crosslinks between the HA chains. The reaction between HA and DMTMM has been investigated and optimized in regard to degree of substitution (DS). Analysis using SEC-LC-UV demonstrated that the reaction was successful in coupling benzylamine to HA with a DS of 40%. Gel formation was successful using hexamethylene diamine as a crosslinker. Results also show that the reaction can be controlled by either the DMTMM or the amine concentration so that a specific degree of substitution or crosslinking is achieved. The stability of DMTMM has also been examined, and degradation studies of DMTMM in H2O at 50 °C with 1H NMR analysis show that 11% of the starting material remains after 48 hours. The reaction has proven to be an effective alternative to other modification methods with cheap reagents, simple procedures and the ability to control the amount of modification. Further investigations are nonetheless required in order to determine the full potential the DMTMM-activated amidation of HA.