Conformationally stable peptide macrocycles assembled using the Petasis borono-Mannich reaction.

Chem Commun (Camb)

Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.

Published: August 2019


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

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.

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc05934bDOI Listing

Publication Analysis

Top Keywords

peptide macrocycles
8
petasis borono-mannich
8
borono-mannich reaction
8
endocyclic amine
8
conformationally stable
4
stable peptide
4
macrocycles assembled
4
assembled petasis
4
reaction macrocyclization
4
macrocyclization linear
4

Similar Publications

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 PDF

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 PDF

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 PDF

Chemistry and Biology of Ustiloxin Analogs as Mycotoxins.

J 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 PDF

Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1.

Eur 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.

View Article and Find Full Text PDF