RESUMEN
The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.
RESUMEN
The Bcl-2 family members rigorously regulate cell endogenous apoptosis, and targeting anti-apoptotic members is a hot topic in design of anti-cancer drugs. At present, FDA and EMA have approved Bcl-2 inhibitor Venetoclax (ABT-199) for treating chronic lymphocytic leukemia (CLL). However, inhibitors of anti-apoptotic protein BCL2A1/Bfl-1 have not been vigorously developed, and no molecule with ideal activity and selectivity has been found yet. Here we review the biological function and protein structure of Bfl-1, discuss the therapeutic potential and list the currently reported inhibitory peptides and small molecules. This will provide a reference for Bfl-1 targeting drug discovery in the future.
Asunto(s)
Antineoplásicos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Sulfonamidas/farmacología , Antineoplásicos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Antígenos de Histocompatibilidad Menor/metabolismo , Modelos Moleculares , Estructura Molecular , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Sulfonamidas/químicaRESUMEN
To recover a nitrogen resource from high-ammonia-nitrogen wastewater, two amphitrophic hydrogen-oxidizing bacteria (HOB), Paracoccus denitrificans Y5 and P. versutus D6, capable of nitrogen assimilation for single-cell protein (SCP) production were isolated. These two HOB strains could grow autotrophically with H2 as an electron donor, O2 as an electron acceptor, CO2 as a carbon source, and ammonia nitrogen (NH4+-N) as a nitrogen source. The cell molecular formulas of strains Y5 and D6 determined by autotrophic cultivation were C3.33H6.83O2.58N0.77 and C2.87H5.34O3.17N0.57, respectively. The isolated strains could synchronously remove NH4+-N and organic carbon and produce SCP via heterotrophic cultivation. The rates of removal of NH4+-N and soluble chemical oxygen demand reached 35.47 and 49.04%, respectively, for Y5 under mixotrophic cultivation conditions with biogas slurry as a substrate. SCP content of strains Y5 and D6 was 67.34-73.73% based on cell dry weight. Compared with soybean meal, the SCP of Y5 contained a variety of amino acids.