title: Effects of carbohydrate polymers applicable in saliva substitutes on the anti-Candida activity of a histatin-derived peptide.
abstract: The effects of polymers applicable in saliva substitutes on the anti-Candida activity of the cationic antimicrobial peptide dhvar1 were investigated. Dhvar1 is a derivative of the 14 C-terminal amino acids of histatin 5. The effects of the following polymers were tested: uncharged hydroxyethylcellulose (HEC), negatively charged xanthan (XG) and three types of negatively charged carboxymethylcellulose (CMC) of identical mass but different degrees of carboxylic acid-group substitution (DS). The effects were tested at pH 4.0, 7.0 and 8.5 in a killing assay. HEC had no effect at any pH tested; XG and the three types of CMC caused a decrease in activity at increasing concentrations. Within the CMC group, inhibition increased slightly with increasing DS. These results suggest that the reduction in activity associated with these polymers is the result of electrostatic interaction between the positively charged peptides and the negatively charged polymers. In the absence of polymers, no effect of pH was found on the activity of dhvar1. In the presence of the charged polymers XG and CMC, lowering the pH from 7.0 to 4.0 resulted in a decrease of dhvar1 activity. It was concluded that, with respect to the retention of activity, HEC is the most appropriate polymer for use in combination with dhvar1. However, for use in saliva substitutes XG seems more suitable because of its rheological properties. If XG or CMC are to be used, their reductive effect on the anti-Candida activity of dhvar1 should be compensated for by increasing the peptide dose.
authors.affiliation: Section of Oral Biochemistry, Department of Dental Basic Sciences, Academic Centre for Dentistry Amsterdam (ACTA), Van der Boechorststraat 7, Amsterdam, The Netherlands.
authors.forename: Anita L A
authors.initials: AL
authors.lastname: Ruissen
authors.forename: Jasper
authors.initials: J
authors.lastname: Groenink
authors.forename: Cock H
authors.initials: CH
authors.lastname: Lommerse
authors.forename: Wim
authors.initials: W
authors.lastname: Van 't Hof
authors.forename: Enno C I
authors.initials: EC
authors.lastname: Veerman
authors.forename: Arie V
authors.initials: AV
authors.lastname: Nieuw Amerongen
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002241:Carbohydrates / Q000494:pharmacology; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry / Q000494:pharmacology; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D054808:Histatins; D006801:Humans; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments; D011108:Polymers / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology; D012212:Rheology; D012464:Saliva, Artificial / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000494:pharmacology; D014783:Viscosity
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D002241:Carbohydrates; C068075:HTN3 protein, human; D054808:Histatins; D010446:Peptide Fragments; D011108:Polymers; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D012464:Saliva, Artificial; D012471:Salivary Proteins and Peptides; D002482:Cellulose; C002283:hydroxyethylcellulose; D002266:Carboxymethylcellulose Sodium; C002563:xanthan gum