title: Inhibition of pepsin activity by alginates in vitro and the effect of epimerization.
abstract: Alginates are versatile biopolymers used extensively in the food, textile and pharmaceutical industries. One of the major uses is in the treatment of reflux disease and here we investigate whether alginates can influence pepsin activity, a major aggressor in reflux disease. The primary uronic acid structure of alginates can be altered using epimerase technology and we test tailor-made alginates to identify the optimal structure for pepsin inhibition. Pepsin activity in the presence of alginates was studied using an in vitro N-terminal assay and enzyme kinetics using a chromagenic peptide. The data described showed clearly that alginates were capable of concentration dependently reducing the activity of pepsin in a non-competitive manner, in vitro. This was variable between different alginates of wide ranging structure and size with positive correlation with alternating sequences of mannuronic and guluronic acid. We hypothesize that alginates may have a more extensive role in the treatment of reflux disease by inhibiting pepsin, a damaging component of the refluxate.
authors.affiliation: Technostics Ltd., The Deep Business Centre, Kingston Upon Hull, East Yorkshire HU1 4BG, UK. Vicki.strugala@technostics.com
authors.forename: Vicki
authors.initials: V
authors.lastname: Strugala
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Kennington
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Campbell
authors.forename: Gudmund
authors.initials: G
authors.lastname: Skjåk-Braek
authors.forename: Peter W
authors.initials: PW
authors.lastname: Dettmar
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000302:isolation & purification; D002238:Carbohydrate Epimerases / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007700:Kinetics; D010434:Pepsin A / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014783:Viscosity
chemical_list: D000464:Alginates; D010434:Pepsin A; D002238:Carbohydrate Epimerases