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

• Published in: Marine drugs 2019-09, Vol.17 (10), p.542
• Main Authors: Sintsova, Oksana, Gladkikh, Irina, Kalinovskii, Aleksandr, Zelepuga, Elena, Monastyrnaya, Margarita, Kim, Natalia, Shevchenko, Lyudmila, Peigneur, Steve, Tytgat, Jan, Kozlovskaya, Emma, Leychenko, Elena
• Format: Article
• Language: English
• Subjects: alpha-Amylases - antagonists & inhibitors; Amino Acid Sequence; amylase inhibitors; Amylases; Analogs; Animals; Antiinfectives and antibacterials; Antimicrobial agents; Bacteria; beta-Defensins - pharmacology; Biological activity; Blood Glucose - drug effects; Cell membranes; Cnidaria; Cnidarian Venoms - pharmacology; Cytoplasmic membranes; defensin; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Heteractis magnifica; Humans; Inhibitors; Ion channels; Marine invertebrates; Membranes; Mucus; Mucus - chemistry; Pancreas; Peptides; Peptides - pharmacology; Recombinants; Saliva; sea anemones; Sea Anemones - chemistry; Spectrum analysis; Stability; Venom; α-Amylase
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17100542

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 mucus, which shares 84% sequence identity with helianthamide from . 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.