Alkyne Amino Acids for Click Chemistry and other Conjugations:

Alkyne Amino Acids for Click Chemistry and other Conjugations:

Published on 22/06/2020

Alkyne amino acids allow for Click conjugations and other types of chemistry. Read more about alkyne-functionalized amino acids and our related products.

Alkyne functions can undergo an intramolecular Cu(I) or Cu(0) catalzyed 1,3-dipolar cycloaddition (CuAAC) upon reaction with azido groups. Developed by K. Barry Sharpless and Morton Meldal, this type of chemical transformation was quickly dubbed “Click Chemistry”, and has since become a widely used reaction orthogonal to many other types of chemistry in different kinds of applications. Due to its high thermodynamic driving force, which is usually greater than 20 kcal/mol, the click reaction typically proceeds rapidly to completion and tends to be highly selective.

Iris Biotech offers a variety of azido and alkyne amino acids. They can be incorporated into biomolecules by recombinant syntheses, particularly by non-neutral protein translation using the amber-suppression-based orthogonal system, or by chemical reactions, e.g. by solid phase peptide synthesis. Furthermore, alkyne functions can be utilized for a photoinduced (λmax 365 nm) free-radical hydrothiolation double addition reaction as shown for the addition of two molecules of 1-Thio-β-D-glucose to a Cysteine containing peptide fragment (Regnault et al. Bioorg Med Chem 2014).

Propargyloxycarbonyl, commonly abbreviated as Poc or Pryoc, can either be used as alkyne component for standard Click conjugation or for copper-free Diels-Alder type Click reactions in combination with tetrazine linkers. It can also be used as an unusual protecting group for amines, hydroxy functions, or as ester being stable to neat TFA. Deprotection can be achieved at ambient temperature with Co2(CO)8 in TFA:DCM. Cleavage using other transition metals like palladium have also been reported (Fukase et al. Tetrahedron Letters 1999).

Tris(benzyltriazolylmethyl)amine (TBTA; RL-2010) stabilizes copper(I) towards oxidation in solution by complex formation and efficiently catalyses quantitative, regioselective Huisgen 1,3-dipolar cycloadditions between alkynes and azides in different aqueous and organic solvents. In case other chemical functions might interfere with copper (I), e.g. phosphate groups of oligonucleotides, the complex forming capabilities of TBTA are the key to a successful Click conjugation. In literature, TBTA is widely used as biochemical tool to tag proteins and enzymes. In this context, please see THPTA (RL-2210), the water-soluble alternative to TBTA.

See the chemical structures of our alkyne substituted derivatives:

→ Interested in further derivatives? Please contact our Custom Synthesis Service!


References:

  • A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes; V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless; Angew Chem Int Ed Engl 2002; 41: 2596-9. https://doi.org/10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4
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