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Macrocyclization of linear peptide precursors using the Petasis borono-Mannich reaction affords a diverse range of macrocycles with an endocyclic amine. Analysis of the corresponding macrocyclic structures underscores that the hydrogen bond between an endocyclic amine and the adjacent amide NH is a powerful control element for conformationally homogenous peptide macrocycles.
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http://dx.doi.org/10.1039/c9cc05934b | DOI Listing |
J Sep Sci
September 2025
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Nifurtimox (NFX) is a chiral drug used for the treatment of Chagas Disease. Little attention has been paid to the enantioselective properties of chiral drugs used for neglected tropical diseases, highlighting the need for further studies in this area. In this work, the enantioselective properties of NFX were carefully investigated by HPLC using different chiral stationary phases (CSPs) and chromatographic modes.
View Article and Find Full Text PDFJ Med Chem
September 2025
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States.
Proteasome inhibitors are effective in treating hematologic cancers but have limited utility in brain tumors due to poor blood-brain barrier (BBB) penetration and metabolic instability. In this study, we developed novel macrocyclic peptide epoxyketone inhibitors with improved drug-like properties. Compounds were screened for cytotoxicity against brain cancer cell lines, permeability (PAMPA-BBB and Caco-2), and metabolic stability.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
Genetically-encoded libraries of peptide-derived macrocycles containing electrophile 'warheads' (cGELs) can be used to identify potent and selective covalent ligands for protein targets. Such cGELs are synthesized either by incorporation of unnatural amino acids that display mild electrophiles on their side chains or by chemical post-translational modification (cPTM) of mRNA or phage-displayed peptide libraries. Here we investigate fundamental barriers to the synthesis of cGELs.
View Article and Find Full Text PDFJ Agric Food Chem
September 2025
Department Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, People's Republic of China.
Ustiloxin analogs, including ustiloxins and phomopsins, are a group of cyclopeptide mycotoxins produced by fungi. They are a 13-membered macrocyclic ring and an ether linkage between tyrosine and isoleucine as the core structure. They are ribosomally synthesized and post-translationally modified peptides.
View Article and Find Full Text PDFEur J Med Chem
December 2025
Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438, Frankfurt am Main, Germany; Structural Genomics Consortium, Buchmann Institute for Life Sciences, Goethe-University Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany. Electronic address:
Since the outbreak of SARS-CoV-2 in recent years, our society has become more aware that zoonotic diseases pose a real threat. Therefore, the demand for small molecules that target host proteins, essential for viral entry and replication, has increased as an interesting strategy for the development of antiviral agents, as these agents may be effective against several different pathogens. NAK kinases is one such potential target family because they are involved in a variety of cellular functions, hijacked by viruses to invade host cells, such as clathrin-mediated endocytosis.
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