Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00616651" target="_blank" >RIV/60077344:_____/25:00616651 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1039/d4ob01395f" target="_blank" >https://doi.org/10.1039/d4ob01395f</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d4ob01395f" target="_blank" >10.1039/d4ob01395f</a>
Alternative languages
Result language
angličtina
Original language name
Discovery of nostatin A, an azole-containing proteusin with prominent cytostatic and pro-apoptotic activity
Original language description
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium Nostoc sp. Its structure was established based on the core peptide sequence encoded in the biosynthetic gene cluster recovered from the producing strain and subsequent detailed nuclear magnetic resonance and high-resolution mass spectrometry analyses. NosA, composed of a 30 amino-acid peptide core, features a unique combination of moieties previously not reported in RiPPs: the simultaneous presence of oxazole/thiazole heterocycles, dehydrobutyrine/dehydroalanine residues, and a sactionine bond. NosA includes an isobutyl-modified proline residue, highly unusual in natural products. NosA inhibits proliferation of multiple cancer cell lines at low nanomolar concentration while showing no hemolysis. It induces cell cycle arrest in S-phase followed by mitochondrial apoptosis employing a mechanism different from known tubulin binding and DNA damaging compounds. NosA also inhibits Staphylococcus strains while it exhibits no effect in other tested bacteria or yeasts. Due to its novel structure and selective bioactivity, NosA represents an excellent candidate for combinatorial chemistry approaches leading to development of novel NosA-based lead compounds.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
<a href="/en/project/EH22_008%2F0004624" target="_blank" >EH22_008/0004624: PHOTOMACHINES - Photosynthetic cell redesign for high yields of therapeutic peptides</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Organic & Biomolecular Chemistry
ISSN
1477-0520
e-ISSN
1477-0539
Volume of the periodical
23
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
449-460
UT code for WoS article
001360735500001
EID of the result in the Scopus database
2-s2.0-85210406970