7389-87-9Relevant articles and documents
Synthesis of Imidazole and Histidine-Derived Cross-Linkers as Analogues of GOLD and Desmosine
Sch?del, Nicole,Icik, Esra,Martini, Maike,Altevogt, Luca,Ramming, Isabell,Greulich, Andreas,Baro, Angelika,Bilitewski, Ursula,Laschat, Sabine
supporting information, p. 2260 - 2268 (2021/03/04)
Amino acid derivatives with a central cationic heterocyclic core (e.g., imidazolium) are biologically relevant cross-linkers of proteins and advanced glycation end (AGE) products. Here, imidazolium-containing cross-linkers were synthesized from imidazole or histidine by N-alkylation employing aspartate- and glutamate-derived mesylates as key step. Biological investigations were carried out to probe the biocompatibility of these compounds.
Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)
Chien, Huan-Chieh,Colas, Claire,Finke, Karissa,Springer, Seth,Stoner, Laura,Zur, Arik A.,Venteicher, Brooklynn,Campbell, Jerome,Hall, Colton,Flint, Andrew,Augustyn, Evan,Hernandez, Christopher,Heeren, Nathan,Hansen, Logan,Anthony, Abby,Bauer, Justine,Fotiadis, Dimitrios,Schlessinger, Avner,Giacomini, Kathleen M.,Thomas, Allen A.
supporting information, p. 7358 - 7373 (2018/08/06)
The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.
A novel high-capacity immunoadsorbent with PAMAM dendritic spacer arms by click chemistry
Hu, Xiaoyan,Li, Guangji,Lin, Yinlei
, p. 15726 - 15732 (2018/10/04)
Polyamidoamine (PAMAM) dendrimers, bearing multiple peripheral end groups that can be used as clickable modules, make it possible to bind a large number of small-molecule ligands via click chemistry to prepare high-capacity immunoadsorbents. Thus, an immunoadsorbent with PAMAM dendritic spacer arms possessing pseudo-biospecific affinity for IgG from human plasma, Sep-PAMAM-AA, was designed and prepared by click chemistry using sepharose gel as a support and the amino acids His, Phe and Trp as ligands; two sepharose-based control samples, Sep-triazole-His and Sep-PA, with linear spacer arms were prepared using l-histidine and protein A as ligands, respectively. The ligand density and IgG adsorption performance of Sep-PAMAM-AA from human plasma were measured and evaluated. The influences of the structure and generation number of the PAMAM spacer arms on the performances of the products were also investigated. The results indicate that the immunoadsorbent with PAMAM G3 as a spacer arm and His as a ligand, Sep-G3-His, is the best among the prepared immunoadsorbents. Its ligand density reaches 1.58 mmol g?1 sepharose gel, almost 5-fold higher than that of Sep-triazole-His; its IgG adsorption capacity is 28.43 mg g?1, which is higher than those of Sep-triazole-His and Sep-PA. Moreover, Sep-G3-His exhibits a relatively low level of non-specific adsorption, which indicates that the immunoadsorbents with PAMAM as a spacer arm and His as a ligand are expected to have great application prospects in the field of blood purification.
