Timothy R. Chan

Bio: Timothy R. Chan is an academic researcher from Biogen Idec. The author has contributed to research in topics: Tyrosine kinase & Alkyne. The author has an hindex of 11, co-authored 17 publications receiving 3380 citations. Previous affiliations of Timothy R. Chan include Scripps Research Institute & University of Alberta.

Bioconjugation by Copper(I)-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition

Abstract: The copper-catalyzed cycloaddition reaction between azides and alkynes functions efficiently in aqueous solution in the presence of a tris(triazolyl)amine ligand. The process has been employed to make rapid and reliable covalent connections to micromolar concentrations of protein decorated with either of the reactive moieties. The chelating ligand plays a crucial role in stabilizing the Cu(I) oxidation state and protecting the protein from Cu(triazole)-induced denaturation. Because the azide and alkyne groups themselves are unreactive with protein residues or other biomolecules, their ligation is of potential utility as a general bioconjugation method.

Inhibitors of bruton's tyrosine kinase

Abstract: The present invention provides a compound, solid forms, and compositions thereof, which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same. The present invention also provides methods of making provided compound and solid forms.

Polytriazoles as Copper(I)‐Stabilizing Ligands in Catalysis.

Abstract: Polytriazolylamines were synthesized by the copper(I)-catalyzed ligation of azides and alkynes. The C3-symmetric derivative, TBTA, was shown to be a powerful stabilizing ligand for copper(I), protecting it from oxidation and disproportionation, while enhancing its catalytic activity.

Polymer-Supported Copper(I) Catalysts for the Experimentally Simplified Azide–Alkyne Cycloaddition

Abstract: Tris-(benzyltriazolylmethyl)amine (TBTA), a widely used ligand for the copper-catalyzed azide-alkyne cycloaddition, has been immobilized on a TentaGel resin. Once loaded with copper(I), the resulting air-stable complex acts as an efficient catalyst for the azide-alkyne cycloaddition reaction and prevents contamination of products by copper salts. The immobilized TBTA ligand should find immediate use in the parallel synthesis of compounds for direct screening.

Cu-catalyzed azide-alkyne cycloaddition.

Abstract: The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

Abstract: The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.

The growing applications of click chemistry

Abstract: Click chemistry, the subject of this tutorial review, is a modular synthetic approach towards the assembly of new molecular entities. This powerful strategy relies mainly upon the construction of carbon–heteroatom bonds using spring-loaded reactants. Its growing number of applications are found in nearly all areas of modern chemistry from drug discovery to materials science. The copper(I)-catalysed 1,2,3-triazole forming reaction between azides and terminal alkynes has become the gold standard of click chemistry due to its reliability, specificity and biocompatibility.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Abstract: Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.