A highly efficient method to synthesize diverse symmetrical phosphinic acids with the potential to act as pivotal candidates in the design of HIV-1 protease inhibitors has been developed. Such compounds have been designed based on the enzyme–substrate specificity, and their elongated analogues are expected to demonstrate significant inhibition against the HIV-1 protease with IC50 values in the low nanomolar range. Moreover, a highly efficient esterification protocol with carbohydrates and flavonoids has been devised to address the inherent absorption challenges associated with phosphinic-based drugs. These esters not only exhibit low toxicity but also have the potential to generate flavonoid moieties in situ, which are associated with hepatoprotective effects, or naturally occurring carbohydrate metabolites. The methodology utilizes effective peptide coupling reagents, such as aminium-based TBTU and carbodiimide-based DIC, and affords the target products in excellent to quantitative yields. This research represents a promising avenue for the development of novel HIV-1 protease inhibitors with significant therapeutic benefits.
Yunfei Wang,Wenjie Sun,Yixiao Li,Xuming Zhuang,Chunyuan Tian,Feng Luan,Xiuli Fu
Human immunodeficiency virus (HIV) is still a significant global health concern. Hence, developing a rapid and sensitive method for the detection of HIV is important in early detection. In this paper, we focus on the preparation of a sensitive electrochemical luminescence (ECL) biosensor that uses Ti 3 C 2 T x modified ZIF-8 as an ECL emitter to detect HIV-1 protein. This ECL biosensor used 0.05 M K 2 S 2 O 8 as the co-reactant and conductive carbon black combined with magnetic nanoparticles as the quenching agent. Under the optimized experimental conditions, the relationship was linear in the range from 1 fM to 1 nM (R 2 = 0.993) and the detection limit was 0.3 fM (S/N = 3). Finally, we used the constructed Ti 3 C 2 T x /ZIF-8 nanocomposites to detect HIV-1 in real serum samples and obtained great recoveries. The results demonstrated that this biosensor, which not only exhibited improved electrical conductivity but also demonstrated an excellent ECL response, could be a promising candidate for HIV-1 detection.
危险品化学品经营许可证（带存储）