790692-11-4Relevant academic research and scientific papers
Lacosamide isothiocyanate-based agents: Novel agents to target and identify lacosamide receptors
Ki, Duk Park,Morieux, Pierre,Salomé, Christophe,Cotten, Steven W.,Reamtong, Onrapak,Eyers, Claire,Gaskell, Simon J.,Stables, James P.,Liu, Rihe,Kohn, Harold
supporting information; experimental part, p. 6897 - 6911 (2010/04/24)
(R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults.Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy) propionamide ((R)-9), exhibited excellent seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. 2009 American Chemical Society.
Ring-opening of aziridine-2-carboxamides with carbohydrate C1-O-nucleophiles. Stereoselective preparation of α- and β-O-glycosyl serine conjugates
Ryan, Daniel A.,Gin, David Y.
supporting information; experimental part, p. 15228 - 15229 (2009/03/12)
The stereoselective formation of the α-GalNAc-Ser linkage via the ring opening of aziridine-2-carboxamides with pyranose C1-O-nucleophiles is described. The process is tolerant to the native C2-NHAc group, can be modulated to provide either the α- or β-glycoside through judicious choice of solvent and metal counterion, and is amenable to other classes of O-glycosyl-Ser constructs such as the β-GlcNAc-Ser and α-Man-Ser linkages. This coupling reaction also led to the development of the o-allylbenzyl (ABn) moiety as a new C-terminus carboxyl protective group, which allows for the use of novel methods for N- and C-terminus extension of amino acids following carbohydrate conjugation. Copyright
Site-selective conjugation of thiols with aziridine-2-carboxylic acid-containing peptides
Galonic, Danica P.,Van Der Donk, Wilfred A.,Gin, David Y.
, p. 12712 - 12713 (2007/10/03)
The synthesis and convergent site-selective conjugation of aziridine-2-carboxylic acid-containing peptides with thiols, both in solution and on solid support, are described. The synthesis and use of FmocAzyOH in this capacity demonstrate both the efficient incorporation and tolerance of the Azy moiety in multistep Fmoc solid-phase peptide synthesis (SPPS), as well as the competence of solution and on-bead ligation through a highly regioselective base-promoted aziridine ring-opening process. Copyright
