Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Canuto, Kirley Marques
Suzuki, Brian M
Naman, C Benjamin
Duggan, Brendan M
O'Donoghue, Anthony J
Gerwick, William H
MetadataShow full item record
AbstractMarine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Using mass-spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization. Structure elucidation was facilitated by employing advanced NMR techniques including nonuniform sampling in combination with the 1,1-ADEQUATE experiment. These cyclic peptides are characterized by the presence of several unusual residues including 3-amino-6-hydroxy-2-piperidone and 2-amino-2-butenoic acid, together with a novel vinyl chloride-containing residue. Tutuilamides A-C show potent elastase inhibitory activity together with moderate potency in H-460 lung cancer cell cytotoxicity assays. The binding mode to elastase was analyzed by X-ray crystallography revealing a reversible binding mode similar to the natural product lyngbyastatin 7. The presence of an additional hydrogen bond with the amino acid backbone of the flexible side chain of tutuilamide A, compared to lyngbyastatin 7, facilitates its stabilization in the elastase binding pocket and possibly explains its enhanced inhibitory potency.
CitationACS Chem Biol. 2020 Mar 20;15(3):751-757. doi: 10.1021/acschembio.9b00992. Epub 2020 Jan 28.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstraße 7, 38124 Braunschweig, Germany.
JournalACS chemical biology
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Palstimolide A: A Complex Polyhydroxy Macrolide with Antiparasitic Activity.
- Authors: Keller L, Siqueira-Neto JL, Souza JM, Eribez K, LaMonte GM, Smith JE, Gerwick WH
- Issue date: 2020 Mar 31
- Total Synthesis of the Potent Marine-Derived Elastase Inhibitor Lyngbyastatin 7 and in Vitro Biological Evaluation in Model Systems for Pulmonary Diseases.
- Authors: Luo D, Chen QY, Luesch H
- Issue date: 2016 Jan 15
- Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides.
- Authors: Matthew S, Ross C, Rocca JR, Paul VJ, Luesch H
- Issue date: 2007 Jan
- Pitipeptolides A and B, new cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula.
- Authors: Luesch H, Pangilinan R, Yoshida WY, Moore RE, Paul VJ
- Issue date: 2001 Mar
- Isolation and structure determination of lyngbyastatin 3, a lyngbyastatin 1 homologue from the marine cyanobacterium Lyngbya majuscula. Determination of the configuration of the 4-amino-2,2-dimethyl-3-oxopentanoic acid unit in majusculamide C, dolastatin 12, lyngbyastatin 1, and lyngbyastatin 3 from cyanobacteria.
- Authors: Williams PG, Moore RE, Paul VJ
- Issue date: 2003 Oct