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Biologically active compound against type 2 diabetes was received in PIBOC by FEFU graduates.

March 31st, 2020

Scientists have studied the natural toxin magnificamide isolated from the venom of the sea anemone Heteractis magnifica, and synthesized its analog, which can become an active ingredient of new drugs for the treatment of metabolic disorders including prediabetes and type 2 diabetes. A new compound is 1000 times more effective than acarbose, the basic component for some modern hypoglycemic drugs reducing blood sugar. A related article was published in Doklady Biochemistry and Biophysics.

Artificial synthesis of the natural magnificamide analog was carried in the G.B. Elyakov Pacific Institute of Bioorganic Chemistry (PIBOC, a research Institute within Far East Branch of Russian Academy of Sciences, FEB RAS) with the participation of young scientists of School of Natural Sciences, Far Eastern Federal University (FEFU, Vladivostok, Russia).

"Sea anemones are ancient marine predators spending most of their life attached to hard surfaces such as rocks and boulders. During evolution, they have accumulated a rich arsenal of peptide toxins that are part of their venoms. In the venom secret of Heteractis magnifica marine anemone, we found a powerful peptide that inhibits the activity of alpha-amylases, important enzymes involved in the humans' digestion process and breaks down the decomposition of starch into smaller components, including glucose, which then enters the bloodstream. Using biotechnology and genetic engineering methods, we synthesized an analog of the natural toxin, magnificamide. During laboratory studies, the recombinant peptide showed high potential, even in extremely small doses effectively suppressing the activity of alpha-amylases. We hope that the compound will become a candidate for the role of the active ingredient of new drugs for the treatment of diabetes", said Aleksandr Kalinovskii, FEFU "Chemistry" second-year graduate, Junior Researcher at the Laboratory for Molecular Pharmacology and Biomedicine PIBOC.

According to the young scientist, it's too early to discuss the development of the ready-to-use drug. First, it is necessary to verify the efficacy and safety of recombinant magnificamide for the human body in vivo (on living organisms, e.g. mice). During this, it may be necessary to develop a more effective compound based on the received one. Only after that, scientists will be able to start clinical trials.

Type 2 diabetes is a metabolic disorder when a violation of the insulin interaction with tissue cells resulted in an increased amount of glucose in the blood. The reason may be a sedentary lifestyle, overeating and an unbalanced diet. Type 2 diabetes affects about 8 percent of the world's adult population. In addition, the disease is increasingly diagnosed in children and adolescents.

The alpha-amylase blocking mechanism underlies some anti-type 2 diabetes drugs. Their mechanism is to slow down the decomposition of starch during digestion and thus prevent the glucose contained in it from entering the blood of diabetic patients.

Modern drugs based on acarbose, used in medical practice to suppress alpha-amylases, have limited effectiveness and a number of side effects. Scientists around the world continue to look for new compounds that can become the active ingredient of the drugs for type 2 diabetes therapy.

Young researchers from FEFU students, undergraduates and graduates together with PIBOC Laboratory for Molecular Pharmacology and Biomedicine and PIBOC Laboratory for Peptide Chemistry are investigating toxins from the sea anemone venoms. Many of these marine compounds have a broad biological activity and can potentially become the basis for new drugs, including the drugs for antitumor and type 2 diabetes therapy.

More information:
O. V. Sintsova et al. Magnificamide Is a New Effective Mammalian α-Amylase Inhibitor, Doklady Biochemistry and Biophysics (2020). DOI: 10.1134/S1607672919060097

Provided by Far Eastern Federal University

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