Synthesis and Biological Evaluation of a Library of AGE‐Related Amino Acid Triazole Crosslinkers

Abstract

Three N‐Boc‐protected amino acids, l‐serine, l‐aspartic, and l‐glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann‐Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu‐catalyzed click reaction provided a library of amino acid based triazoles, which were further N‐methylated to triazolium iodides or deprotected and precipitated as free amino acid triazole dihydrochlorides. The biological properties of all derivatives were investigated by cytotoxicity assay (against L929 mouse fibroblasts) and broth microdilution method (E. coli ΔTolC and S. aureus). First results reveal complete inactivity for triazolium iodides with cell viabilities and microbial growths nearly 100 %, indicating them as possible analogs of advanced glycation endproducts (AGEs).

Modulating chitin synthesis in marine algae with iminosugars obtained by SmI2 and FeCl3-mediated diastereoselective carbonyl ene reaction

“…In order to investigate the biological properties of the synthesized iminosugars (Scheme 7), they were submitted to a cell viability assay using the murine fibroblast cell line L929 and the AlamarBlue assay. 72 This assay is based on the reduction of resazurin to fluorescent resorufin by viable cells. Cells were incubated with the compounds for 72 h, before the resazurin solution was added.…”

“…The cytotoxicity assay was largely performed as already previously published. 72 In brief: Resazurin (AlamarBlue) was used to determine viability of cells which are capable of reducing it to the fluorescent resorufin. 2 μL of serial dilutions of the test compounds were added to 60 μL aliquots of a cell suspension (15 600 mL −1 ) in 96-well half area microplates (Costar 3697).…”

“…In order to investigate the biological properties of the synthesized iminosugars (Scheme 7), they were submitted to a cell viability assay using the murine fibroblast cell line L929 and the AlamarBlue assay. 72 This assay is based on the reduction After an incubation time of 3 h the fluorescence was determined (λ ex 540 nm, λ em 600 nm). Data were normalised with respect to viability of DMSOtreated cells (100% viability).…”

Synthesis of non-natural amino acids as covalent inhibitors for protein-protein interactions.

“…An N-Boc protected amino acid was transformed to ethyl esters (Scheme 3.8). 144,145 This method gave 86% & 93% in yields. In light of our success with protecting both the amine and carboxylic acid group, we attempted the two-chamber reactor protocol for the installation of the SO2F group on compound 3.13.…”

“…NMR (500 MHz, DMSO-d6): δ 7.63 (d, J = 7.1 Hz, 2H), 7.26 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 2H), 4.18 -4.12 (m, 1H), 3.61 (s, 3H), 2.96 (dd, J = 13.6, 4.9 Hz, 1H), 2.80 (dd, J = 13.6, 3.2 Hz, 1H), 1.31 (s, 9H).13 C NMR (125 MHz, DMSO-d6): δ 172.8, 155.8, 137.9, 137.4, 132.0, 92.7, 78.8, 55.3, 52.3, 36.4, 28.5 ppm. HRMS (ESI) m/z 428.0337 (calcd for C15H20NO4NaI [M+Na] + 428.0335).4.2.3 General procedure C: The SN2 O-Alkylation of amino acid144,145 method was used with modification. To a cold solution of an N-Boc protected aliphatic amino acid in DMF (8.75 mL), K2CO3 (1 mmol) is added, and the reaction mixture is stirred at 0 °C 10 minutes.…”