Magnificamide, a β-Defensin-Like Peptide from the Mucus of the Sea Anemone Heteractis magnifica, Is a Strong Inhibitor of Mammalian α-Amylases

Abstract

Sea anemones’ venom is rich in peptides acting on different biological targets, mainly on cytoplasmic membranes and ion channels. These animals are also a source of pancreatic α-amylase inhibitors, which have the ability to control the glucose level in the blood and can be used for the treatment of prediabetes and type 2 diabetes mellitus. Recently we have isolated and characterized magnificamide (44 aa, 4770 Da), the major α-amylase inhibitor of the sea anemone Heteractis magnifica mucus, which shares 84% sequence identity with helianthamide from Stichodactyla helianthus. Herein, we report some features in the action of a recombinant analog of magnificamide. The recombinant peptide inhibits porcine pancreatic and human saliva α-amylases with Ki’s equal to 0.17 ± 0.06 nM and 7.7 ± 1.5 nM, respectively, and does not show antimicrobial or channel modulating activities. We have concluded that the main function of magnificamide is the inhibition of α-amylases; therefore, its functionally active recombinant analog is a promising agent for further studies as a potential drug candidate for the treatment of the type 2 diabetes mellitus.

A Review of Toxins from Cnidaria

“…Research on the TRPV1 inhibitors has continued on this species, from which the other three homologous peptides, τ-SHTX-Hcr2c (APHC2), τ-SHTX-Hcr2d (APHC3) and HCRG21, have been isolated [ 126 , 129 ]. These three peptides showed analgesic activity in an in vivo heat stimulation model [ 130 , 139 ]…”

“…Helianthamide, a potent inhibitor of human pancreatic α-amylase produced by the Caribbean Sea anemone Stichodactyla helianthus , is the first representative of a new group of amylase inhibitors that was isolated in 2016 [ 175 ], while Magnificamide is the second representative of such inhibitors. Both peptides appear to be promising compounds to manage obesity and type 2 diabetes [ 139 ]. The biological relevance of the presence of α-amylase inhibitors in the Cnidaria venoms remains largely unexplained.…”

“…The biological relevance of the presence of α-amylase inhibitors in the Cnidaria venoms remains largely unexplained. It is hypothesized that inhibition of the α-amylase activity intervenes with the metabolism of carbohydrates, a major source of energy for many organisms [ 139 ].…”

“…In particular, helianthamide was isolated from the Caribbean Sea anemone Stichodactyla helianthus and showed to adopt a β-defensin fold and bind into and across the amylase active site (with Ki = 10 pM) [ 152 ]. Magnificamide, recently isolated from sea anemone Heteractis magnifica , shared 84% sequence identity with helianthamide and inhibited porcine pancreatic and human saliva α-amylases with Ki’s equal to 0.17 ± 0.06 nM and 7.7 ± 1.5 nM, respectively, showing to be another potential drug candidate for diabetes treatment [ 139 ]…”

Selected Papers from the Third International Symposium on Life Science

“…Magnificamide, the major α-amylase inhibitor, comprising of 44 amino acid residues (4770 Da), was isolated from the sea anemone Heteractis magnifica mucus. Sintsova and colleagues from PIBOC and University of Lueven, Belgium, have reported that the recombinant magnificamide inhibits porcine and human saliva α-amylases in low nanomolar concentrations and could be considered as a promising drug candidate for the type 2 diabetes treatment [8].…”