Six seongsanamides were isolated from the culture broth of Bacillus safensis KCTC 12796BP, and their structures were elucidated by spectroscopic data analysis combined with Marfey's method, electronic circular dichroism calculations, and biosynthetic gene cluster analysis. Compounds 1-4 were bicyclic peptides with isodityrosine residues; 5 and 6 were monocyclic peptides. Only the bicyclic seongsanamides inhibited degranulation and LTC/PGD generation in IgE/Ag-stimulated bone marrow-derived mast cells. Oral administration of 1 suppressed mast cell-dependent passive cutaneous anaphylaxis reaction.
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http://dx.doi.org/10.1021/acs.orglett.8b03293 | DOI Listing |
Bioanalysis
January 2025
Quantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.
Background: The Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker. Zelenectide pevedotin is currently being investigated in a Phase 1/2 (Duravelo-1, NCT04561362) clinical trial to determine safety and efficacy in patients with tumors associated with Nectin-4 expression. A simple regulated bioanalytical assay was developed to quantify intact zelenectide pevedotin in patient plasma samples.
View Article and Find Full Text PDFBMC Pulm Med
January 2025
Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, 7618868367, Iran.
Background: Paraquat (PQ) is a widely used pesticide, can cause severe intoxication and respiratory failure. Myrtenol (Mrl), an essential oil derived in various plants, exhibits several biological properties, including anti-inflammatory and antioxidant activities. This study aims to investigate the protective potential of Mrl against oxidative stress and inflammation caused by PQ exposure.
View Article and Find Full Text PDFChemistry
January 2025
Research School of Chemistry, Australian National University, Canberra, ACT, 2601, Australia.
Constrained peptides possess excellent properties for identifying lead compounds in drug discovery. While it has become increasingly straightforward to discover selective high-affinity peptide ligands, especially through genetically encoded libraries, their stability and bioavailability remain significant challenges. By integrating macrocyclization chemistry with bismuth binding, we generated series of linear, cyclic, bicyclic, and tricyclic peptides with identical sequences.
View Article and Find Full Text PDFBiochemistry
January 2025
Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Janustatin A is a potently cytotoxic polyketide alkaloid produced at trace amounts by the marine bacterial plant symbiont . Its biosynthetic terminus features an unusual pyridine-containing bicyclic system of unclear origin, in which polyketide and amino acid extension units appear reversed compared to the order of enzymatic modules in the polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line. To elucidate unknown steps in heterocycle formation, we first established robust genome engineering tools in .
View Article and Find Full Text PDFBiomedicines
December 2024
Department of Chemistry and Chemical Biology, University of New Mexico, 346 Clark Hall, 300 Terrace St. NE, Albuquerque, NM 87131, USA.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a growing class of natural products biosynthesized from a genetically encoded precursor peptide. RiPPs have attracted attention for the ability to generate and screen libraries of these compounds for useful biological activities. To facilitate this screening, it is useful to be able to do so with the leader peptide still present.
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