Design, synthesis, and biological activity of novel triazole amino acids used to probe binding interactions between ligand and neutral amino acid transport protein SN1

Abstract

Novel triazole amino acids were synthesized as probes to investigate ligand-protein binding interactions of the neutral amino acid transporter SN1. The bonding hypothesis to be tested was that the side chains of endogenous substrates are acting as H-bond acceptors. Although limited inhibition of (3)H-L-glutamine uptake by SN1 expressing oocytes was observed, the synthetic compounds show a trend that suggests a hydrogen bond interaction just outside the endogenous ligand binding pocket.

1,2,3‐Triazoles in Peptidomimetic Chemistry

“…[82,83] In one study, Gajewski et al investigated the use of such structures as a basis for inhibitors of the amino acid system N transport protein SN1. [82] An overlay of the energy-minimised structures of the natural substrates (l-glutamine, l-asparagine and l-histidine) of SN1, suggested an amino acid with a 1,4-substituted triazole in the side chain would be able to provide key hydrogen-bonding interactions with the protein (58, Scheme 21). The fully protected triazole amino acids 57 were thus prepared by CuAAC of β-azido alanine 56 with a range of acetylenes under standard conditions.…”

1,2,3-Triazolium Salts as a Versatile New Class of Ionic Liquids

“…The product was obtained as a colour less solid (mp 91 o C). A similar Cucatalyzed cycloaddition was reported for the synthesis and biochemical application of a lower homologue of 53 (Gajewski, Seaver et al 2007). Unexpectedly, the triazolium ionic liquid tagged catalyst 53 wherein a noncyclic -amino acid unit was found instead of proline failed to give any enantioselectivity.…”

(R)-α-Aminoadipic Acid: A Versatile Precursor for the Synthesis of D-Amino Acids

“…Keeping in view the importance of triazole system [25] and with this azide intermediate in our hands, we performed click reactions using CuSO 4 /ascorbate and Cp*Ru(PPh 3 ) 2 Cl 2 as catalysts for the synthesis of 1,4- and 1,5-disubstituted triazole amino acid derivatives. Treatment of azide 8 with alkynes proceeded smoothly in the presence of a catalytic amount of CuSO 4 and sodium ascorbate in a 10% solution of DMSO in water to produce 1,4-disubstituted-1,2,3-triazole derivatives 11 and 12 in good yields, respectively.…”