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.

Design, Synthesis, Biological Evaluation, and Docking Studies of (S)‐Phenylalanine Derivatives with a 2‐Cyanopyrrolidine Moiety as Potent Dipeptidyl Peptidase 4 Inhibitors

“…The ( S )‐ N ‐Boc‐azidoalanine 12 was easily accessible in two steps starting from the commercially available ( S )‐ N ‐Boc‐serine following a reported procedure . Click reaction of ( S )‐ N ‐Boc‐azidoalanine 12 with phenylacetylene or substituted phenylacetylene in the presence of catalytic amount of CuSO 4 ·5H 2 O and sodium ascorbate in EtOH afforded the corresponding triazolyl amino acid compounds 13a–c in good yields . The triazolyl amino acid compounds 13a–c were then condensed with ( S )‐pyrrolidine‐2‐carbonitrile hydrochloride utilizing EDC and HOBt in CH 2 Cl 2 to afford compounds 14a–c .…”

Concise CuI-Catalyzed Azide–Alkyne 1,3-Dipolar Cycloaddition Reaction Ligation Remarkably Enhances the Corrosion Inhibitive Potency of Natural Amino Acids for Mild Steel in HCl

“…Preparation of functional bis-amino acid derivatives wherein the coupling position principally points to separately the backbone or the side chain of each amino acid subunit via Cue-AAC has been achieved by several independent research groups. − In contrast, we apply here an alternative synthetic strategy addressing the ligation of the side chain of one amino acid to the backbone of the other …”

“…The Cu I -catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction, , which has just been shortened to “Cue-AAC”, represents the best paradigm of click chemistry to date and has fulfilled the efficient creation of countless chemical tools useful in probing into the various branching fields of the chemical science . Recently, considerable effort has been devoted to the construction of triazolyl peptidomimetics via Cue-AAC for the investigation of peptide conformations. , Meanwhile, considering the intrinsic merits of the triazole such as its physicochemical resemblance to natural amide bond, nontoxicity, and stability under stringent conditions, some triazole-linked small-molecule amino acid analogues have been prepared serving as protein ligands and fluorescent probes. − …”

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides

“…Serine is a convenient precursor for the synthesis of the azido derivative of alanine. Several different methods were previously developed for introducing the azido moiety to a serine derivative: (i) ring opening of cyclic N ‐(phenyl fluoride) serine sulfamidate , (ii) opening of ( S )‐3‐amino‐2‐oxetanone , (iii) mild bromination of the hydroxyl group followed by azidation , (iv) Mitsunobu reaction treatment with triphenylphosphine (PPh 3 ), hydrazoic acid and azodicarboxylate , and (v) activation of the hydroxyl group by mesyl chloride (MsCl) or tosyl chloride , followed by substitution with sodium azide. In addition, the synthesis of azidoalanine starting from N ‐protected asparagine represents a different but straightforward approach.…”