A bioactive polypeptide from sugarcane selectively inhibits intestinal sucrase.

Human sucrase enzyme is a key therapeutic target for type 2 diabetes. While sugarcane sucrase inhibitor (sucinh)
modulates invertase activity thereby accumulates sucrose. Molecular level understanding of sucinh towards
mammalian α-glucosidases is scarce. The interaction of sucinh with human sucrase was identified and the association of these proteins was confirmed using co-purification, co-immunoprecipitation and pull-down assay. In
addition, microscale thermophoresis assay showed that sucinh has a tight binding with sucrase (Kd =
4.77 nM) and a better affinity over acarbose. Collectively, in vitro, ex vivo and in silico data revealed that sucinh
is selective for intestinal sucrase. The M region (H5/6 loop) of sucinh identified at the protein-protein interface
is shown to have high affinity over N and C regions. Whereas, the biolayer luminescent imaging and microscale
thermophoresis on the synthetic peptide of 28 amino acids of M region has a weak dose-dependent binding with
sucrase. However, the synthetic peptide did not show substantial inhibition of sucrase and amylase activities at
low concentration. Naturally derived carbohydrate mimics were shown to have a positive impact at the in vitro
conditions. The insights obtained in this study give clues towards a new class of bioactive therapeutic peptides
for α-glucosidases. A new horizon towards polypeptides derived from food sources emerge as a promising strategy for dietary interventions for prediabetic conditions.