PAZ320, a mixture of two galactomannans (GMα and ( ίΜΡβ ), is being developed to treat diabetes and inflammatory diseases. Both GMα and GMβ) have a β(1→4) mannan backbone, with a high density of α(1→6)linked galactose units. When ingested by diabetic patients, PA/320 reduces the magnitude of postprandial glucose excursions. PA/320 functions by binding to enzymes that hydroly/.e starch in the gastrointestinal track and thereby reduces steady-state concentrations of low molecular weight sugars like glucose. PA/320 binds to the a-amylase enzyme from human and porcine sources and thereby attenuates the rate of amylase-mediated hydrolysis of α(1→4)-linked glucose polymers (starch and maltohexaose). We found that PAZ320 at 2.5 mg/ml inhibits amylase activity with starch by about 45%, a level of inhibition that is comparable to that from acarbose at 0.1 3 mg/ml. In addition, we found that the GMα component of PAZ320 is about 5 -fold more active than GMβ. Both GMs also act to "unfold" the coiled structure of starch with no effect on their inhibitory potency towards amylase. On the other hand, part of the inhibitory effect from GMα in vitro arises from its effect on increasing solution viscosity.Linvention concerne PAZ320, un mélange de deux galactomannanes (GMα et GMβ) développé pour traiter le diabète et des maladies inflammatoires. À la fois GMα et GMβ ont un squelette de mannane bêta (1 → 4), avec une densité élevée dunités de galactose liés à alpha (1 → 6). Lorsquil est ingéré par des patients diabétiques, PA320 réduit lamplitude des excursions glycémiques postprandiales. PA320 fonctionne en se liant à des enzymes qui hydrolysent lamidon dans le tractus gastro-intestinal et, de ce fait, réduit les concentrations à léquilibre de sucres de faible poids moléculaire tels que le glucose. PA320 se lie à lenzyme a-amylase dorigines humaine et porcine et atténue ainsi la vitesse de lhydrolyse amylasique de polymères de glucose liés à apha(1 → 4) (amidon et maltohexaose). Nous a
