The incorporation of bactericidal properties into textiles is a widely sought-after aspect, and silver nanoparticles (AgNPs) can be used for this. Here, we evaluate a strategy for incorporating AgNPs into a cotton fabric. For this purpose, a bactericidal textile coating based on a composite of AgNPs and kappa-carrageenan (k-CA) was proposed. The composite was obtained by heating the silver precursor (AgNO₃) directly in k-CA solution for green synthesis and in situ AgNPs stabilization. Cotton substrates were added to the heated composite solution for surface impregnation and hydrogel film formation after cooling. Direct synthesis of AgNPs on a fabric was also tested. The results showed that the application of a coating based on k-CA/AgNPs composite can achieve more than twice the silver loading on the fabric surface compared to the textile subjected to direct AgNPs incorporation. Furthermore, silver release tests in water showed that higher Ag⁺ levels were reached for k-CA/AgNPs-coated cotton. Therefore, inoculation tests with the bacteria Staphylococcus aureus (SA) using the agar diffusion method showed that samples covered with the composite resulted in significantly larger inhibition halos. This indicated that the use of the composite as a coating for cotton fabric improved its bactericidal activity against SA.

2024-01-23·Annual review of pharmacology and toxicology

Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance

Review

作者: Jang, Hyunbum ; Nussinov, Ruth

Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-RasG12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-RasG12Cwith a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding growth of insensitive cell clones, and proliferation. Statistics confirm the expectation that most resistance-related mutations are in cis, pointing to the high probability of cooperative, same-allele effects. In addition to targeted Ras inhibitors and drug combinations, bifunctional molecules and innovative tri-complex inhibitors to target Ras mutants are also under development. Since the identities and potential contributions of preexisting and evolving mutations are unknown, selecting a pharmacologic combination is taxing. Collectively, our broad review outlines considerations and provides new insights into pharmacology and resistance.

2020-09-01·Cell chemical biology1区 · 生物学

Targeting Endogenous K-RAS for Degradation through the Affinity-Directed Protein Missile System

1区 · 生物学

Article

作者: Röth, Sascha ; Queisser, Markus A ; Konopacka, Agnieszka ; Sapkota, Gopal P ; Macartney, Thomas J ; Chan, Kwok-Ho ; Zhou, Houjiang

K-RAS is known as the most frequently mutated oncogene. However, the development of conventional K-RAS inhibitors has been extremely challenging, with a mutation-specific inhibitor reaching clinical trials only recently. Targeted proteolysis has emerged as a new modality in drug discovery to tackle undruggable targets. Our laboratory has developed a system for targeted proteolysis using peptidic high-affinity binders, called "AdPROM." Here, we used CRISPR/Cas9 technology to knock in a GFP tag on the native K-RAS gene in A549 adenocarcinoma (A549^GFPKRAS) cells and constructed AdPROMs containing high-affinity GFP or H/K-RAS binders. Expression of GFP-targeting AdPROM in A549^GFPKRAS led to robust proteasomal degradation of endogenous GFP-K-RAS, while expression of anti-HRAS-targeting AdPROM in different cell lines resulted in the degradation of both GFP-tagged and untagged K-RAS, and untagged H-RAS. Our findings imply that endogenous RAS proteins can be targeted for proteolysis, supporting the idea of an alternative therapeutic approach to these undruggable targets.

100 项与 K-RAS (Transcell Oncologics) 相关的药物交易

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