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Native Metabolomics Unveils Suomilide Analogs with Potent Trypsin Inhibitory Activity.

Amira Naimi¹, Christoph Ulbricht², Tung Lam Trinh²

¹Institute of Pharmaceutical Biology and Biotechnology, Marburg University, Robert-Koch-Str. 4, 35037 Marburg, Germany.

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|April 1, 2026

Summary

Cyanobacteria produce potent serine protease inhibitors. Researchers discovered new suomilides G and H from Nostoc sp. KVJ20, which effectively inhibit trypsin, highlighting their pharmaceutical potential.

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Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

Area of Science:

Natural Product Chemistry
Biochemistry
Pharmacology

Background:

Cyanobacteria are prolific producers of bioactive compounds, including serine protease inhibitors.
These natural products represent a valuable resource for discovering novel pharmaceutical lead structures.

Purpose of the Study:

To employ native metabolomics for rapid screening of cyanobacterial extracts against trypsin.
To discover and characterize new potent serine protease inhibitors from cyanobacteria.

Main Methods:

Native metabolomics coupled with liquid chromatography-high resolution tandem mass spectrometry (LC-HR-MS/MS).
Isolation and structural elucidation using 1D/2D NMR spectroscopy and Marfey's analysis.
Bioinformatic investigations and competitive bioassays for enzyme inhibition.

Main Results:

Identification of the suomilide family from Nostoc sp. KVJ20 as potent trypsin inhibitors.
Discovery and structural characterization of two new suomilides, G and H, alongside known congeners B and D.
Demonstrated low nanomolar to high picomolar inhibitory concentrations for all four isolated suomilides against trypsin.

Conclusions:

Suomilides represent an exceptionally potent class of serine protease inhibitors.
Cyanobacteria are a rich source for novel drug leads, exemplified by the suomilide family.
The applied metabolomic approach enables rapid discovery of bioactive natural products.