title: Synthesis and antiherpetic activity of carboxymethylated and sulfated hyaluronan derivatives.
abstract: Native high molecular weight hyaluronan (HMW-HA, MW=1×10(6) g/mol) and a thermally degraded low molecular weight hyaluronan (LMW-HA, MW=1.3-1.4×10(5) g/mol) were carboxymethylated providing products with degrees of carboxymethylation (DSCM) of up to 0.8. Sulfation of resulting carboxymethyl hyaluronan (CM-HA) and hyaluronan (HA) was performed by different sulfation procedures enabling the control of the degree of sulfation (DSS) in the obtained new carboxymethyl hyaluronan sulfates (CM-HA-S) and hyaluronan sulfates (HA-S), respectively, in a range between 0.9 and 3.3. Both carboxymethylation and sulfation were found to take place preferentially at the primary hydroxyl groups of HA. The antiviral activity of these synthesized HA derivatives was tested against Herpes simplex virus type 1. Both HA-S and CM-HA-S derivatives with high DSS values of about 3.0 exhibit a strong antiherpetic activity. The CM-HA derivatives were found to be not active and an additional effect of introduced carboxymethyl groups on the antiherpetic activity of CM-HA-S derivatives was not observed. In the case of HA-S, the antiviral efficacy can be correlated with the DSS and becomes stronger with increasing DSS values.
authors.affiliation: INNOVENT e. V., Biomaterials Department, Pruessingstrasse 27B, D-07745 Jena, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Möller
authors.affiliation: Jena University Hospital, Department of Virology and Antiviral Therapy, Hans-Knöll-Strasse 2, D-07745 Jena, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmidtke
authors.affiliation: Friedrich-Schiller-University Jena, Institute of Organic and Macromolecular Chemistry, Humboldtstrasse 10, D-07743 Jena, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Weiss
authors.affiliation: University of Leipzig, Faculty of Medicine, Institute of Medical Physics and Biophysics, Härtelstrasse 16-18, D-04107 Leipzig, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schiller
authors.affiliation: INNOVENT e. V., Analytics Department, Pruessingstrasse 27B, D-07745 Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Pawlik
authors.affiliation: Jena University Hospital, Department of Virology and Antiviral Therapy, Hans-Knöll-Strasse 2, D-07745 Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.affiliation: INNOVENT e. V., Biomaterials Department, Pruessingstrasse 27B, D-07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnabelrauch
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002522:Chlorocebus aethiops; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000494:pharmacology; D008745:Methylation; D018139:Simplexvirus / Q000187:drug effects*; D013431:Sulfates / Q000138:chemical synthesis* / Q000494:pharmacology; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D013431:Sulfates; D006820:Hyaluronic Acid