Inhibition of pepsin activity by alginates in vitro and the effect of epimerization

Inhibition of pepsin activity by alginates in vitro and the effect of epimerization
Received 18 February 2005; revised 16 July 2005; accepted 18 July 2005. Available online 1 September 2005.
Vicki Strugalaa, , , Erika J. Kenningtonb, Robert J. Campbellb, Gudmund Skj¬k-Br kc and Peter W. Dettmara
International Journal of Pharmaceutics
Volume 304, Issues 1-2 , 4 November 2005
aTechnostics Ltd., The Deep Business Centre, Kingston Upon Hull, East Yorkshire HU1 4BG, UK
bReckitt Benckiser Healthcare (UK) Ltd., Dansom Lane, Kingston Upon Hull, East Yorkshire HU8 7DS, UK
cInstitute of Biotechnology, Norwegian University of Science Technology (NTNU), Sem S lands vei 6-8, N-7491 Trondheim, Norway
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.
Keywords: Alginate; Pepsin; Gastroesophageal reflux; Epimerase; Enzyme kinetics
Abbreviations: M, mannuronic acid; G, guluronic acid; GERD, gastro-esophageal reflux disease; 1H NMR, nuclear magnetic resonance; F, molar fraction; SEC-MALLS, size exclusion chromatography-multi angle laser light scattering; TNBS, trinitrobenzenesulphonic acid; [S], substrate concentration; V, initial reaction velocity; Vmax, maximum enzyme velocity; Km, MichaelisÒMenton constant; r, Pearson's correlation coefficient

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