RESUMO
Chemoselective protein modification plays extremely important roles in various biological, medical, and pharmaceutical investigations. Mimicking the mechanism of the chemoselective reaction between natural azaphilones and primary amines, this work successfully simplified the azaphilone scaffold into much simpler 3-acyl-4-pyranones. Examinations confirmed that these slim-size mimics perfectly kept the unique reactivity for selective conjugation with the primary amines including lysine residues of peptides and proteins. The newly developed pyranone tool presents remarkably increased aqueous solubility and compatible second-order rate constant by comparison with the original azaphilone. Additional advantages also include the ease of biorthogonal combinative use with a copper-catalyzed azide-alkyne Click reaction, which was conveniently applied to decorate lysozyme with neutral-, positive- and negative-charged functionalities in parallel. Moderate-degree modification of lysozyme with positively charged quaternary ammoniums was revealed to increase the enzymatic activities.
Assuntos
Lisina , Muramidase , Lisina/química , Indicadores e Reagentes , Peptídeos/química , Aminas , Azidas/química , Química Click , Alcinos/químicaRESUMO
Residue-selective bioconjugation methods for biomolecules are highly sought to expand the scope of their biological and medical applications. Inspired by the mechanism of the generation of natural vinylogous γ-pyridones (vPDNs), we have developed a novel unique azaphilone-based, activation-free primary-amine-selective bioconjugation method for biomolecules. Our strategy allows facile functionalization of primary amine groups in peptides and proteins, including the clinically used therapeutic antibody trastuzumab, by generating a highly stable vPDN linkage. Excellent chemoselectivity toward primary amines also enables the azaphilone derivatives to specifically modify the lipid components of Gram-positive bacteria while bypassing Gram-negative bacteria and mammalian cells. The new method shows significant advantages including chemoselectivity, efficiency, flexibility and biocompatibility, and therefore provides a valuable addition to the current toolbox for biomolecule conjugation.
Assuntos
Aminas/química , Benzopiranos/química , Lipídeos/química , Peptídeos/química , Pigmentos Biológicos/química , Proteínas/química , Piridonas/síntese química , Estrutura Molecular , Piridonas/químicaRESUMO
BACKGROUND: The cotton aphid (Aphis gossypii Glover) is one of the most invasive pests of cotton. Many botanical phytochemicals have a long history as a source of insecticides, and as templates for new insecticides. This study was undertaken to isolate aphicidal compounds from the seeds of Erythrina crista-galli L. using the bioassay-guided isolation method. RESULTS: Three novel and 11 known Erythrina alkaloids were isolated. Erysodine (9), erysovine (10), erysotrine (8) and erythraline (11) showed moderate to excellent aphicidal activity with LD50 values of 7.48, 6.68, 5.13 and 4.67 ng aphid-1 , respectively. The Potter spray tower bioassay gave corresponding LC50 values of 186.81, 165.35, 163.74 and 112.78 µg ml-1 . A unique substructure, which presents an sp3 methylene at C-8, a non-oxygenated site at N-9 and a conjugated dienes group (Δ1,2 and Δ6,7 ), plays a crucial role in the aphicidal activity. Application of erythraline (11) led to different increases in the activities of superoxide dismutase, catalase and glutathione S-transferase. CONCLUSION: The study demonstrated that the Erythrina alkaloids erysodine (9), erysovine (10), erysotrine (8) and erythraline (11) have potential use as botanical aphicides for commercial application, or as templates for the development of new insecticides. © 2017 Society of Chemical Industry.