A bioactive polypeptide from sugarcane selectively inhibits intestinal sucrase

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Human sucrase is a therapeutic target for type 2 diabetes.
• Sugarcane sucrase inhibitor (sucinh) affects invertase activity, impacting sucrose levels.
• Understanding sucinh's interaction with mammalian alpha-glucosidases is limited.

Purpose of the Study:

• To elucidate the molecular interaction between sucinh and human sucrase.
• To evaluate sucinh's potential as a therapeutic agent for alpha-glucosidase-related conditions.
• To explore naturally derived carbohydrate mimics for dietary interventions.

Main Methods:

• Co-purification, co-immunoprecipitation, and pull-down assays to confirm protein association.
• Microscale thermophoresis (MST) to determine binding affinity (Kd).
• In vitro, ex vivo, and in silico analyses to assess selectivity and inhibition.

Main Results:

• Sucinh demonstrated tight binding to human sucrase (Kd = 4.77 nM), exceeding acarbose affinity.
• Sucinh showed selectivity for intestinal sucrase.
• The M region of sucinh exhibited high affinity, though synthetic peptides showed weak binding and minimal inhibition.

Conclusions:

• Sucinh is a selective inhibitor of human intestinal sucrase.
• Naturally derived carbohydrate mimics show potential for in vitro applications.
• This study paves the way for novel bioactive therapeutic peptides and dietary interventions for prediabetic conditions.