1.
Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications.
Zhang, Y, Bi, J, Huang, J, Tang, Y, Du, S, Li, P
International journal of nanomedicine. 2020;:6917-6934
Abstract
Exosomes are nano-sized small extracellular vesicles secreted by cells, carrying nucleic acids, proteins, lipids and other bioactive substances to play a role in the body's physiological and pathological processes. Compared to synthetic carriers such as liposomes and nanoparticles, the endogeneity and heterogeneity of exosomes give them extensive and unique advantages in the field of disease diagnosis and treatment. However, the storage stability, low yield, low purity, and weak targeting of exosomes limit its clinical application. For this reason, further exploration is needed to optimize the above problems and facilitate future functional studies of exosomes. In this paper, the origin, classification, preparation and characterization, storage stability and applications of exosome delivery system are summarized and discussed by searching a large number of literatures.
2.
Increasing the structural coverage of tuberculosis drug targets.
Baugh, L, Phan, I, Begley, DW, Clifton, MC, Armour, B, Dranow, DM, Taylor, BM, Muruthi, MM, Abendroth, J, Fairman, JW, et al
Tuberculosis (Edinburgh, Scotland). 2015;(2):142-8
-
-
Free full text
-
Abstract
High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.
3.
Aptamer-drug conjugation for targeted tumor cell therapy.
Donovan, MJ, Meng, L, Chen, T, Zhang, Y, Sefah, K, Tan, W
Methods in molecular biology (Clifton, N.J.). 2011;:141-52
Abstract
Aptamers developed for applications in cancer therapy can improve the efficacy of drug treatment and enhance molecular imaging. Aptamers for these purposes are generated from SELEX (Systematic Evolution of Ligands by EXponential enrichment), more precisely cell-based SELEX, a process described in detail in this chapter. Experimental applications are also provided for aptamer-based drugs.