Peptide Conjugation via CuAAC ‘Click’ Chemistry

Fuaad, Abdullah Ahmad; Azmi, Fazren; Skwarczynski, Mariusz; Tóth, István

doi:10.3390/molecules181113148

Cited by 94 publications

(65 citation statements)

References 98 publications

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“…Copper-catalyzed azide-alkyne cycloaddition (CuACC) 32 was chosen for oligomerization because of the orthogonality of CuACC chemistry with typical peptide functional and protecting groups. 33–36 Finally, an A 2 + B 2 assembly strategy was selected over an AB strategy in order that the oligomer structure might be more easily altered (by changing out the B 2 co-monomer) and to limit macrocyclization. 34,37 …”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2 strategy

Dehigaspitiya

Suryakiran

Weber

et al. 2015

Tetrahedron Letters

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Oligomers incorporating the tetrapeptide MSH4, the minimum active sequence of melanocyte stimulating hormone, were synthesized by an A2 + B2 strategy involving microwave-assisted copper-catalyzed azide-alkyne cycloaddition. A2 contained an MSH4 core while B2 contained a (Pro-Gly)3 spacer. Soluble mixtures containing compounds with up to eight MSH4 units were obtained from oligomerizations at high monomer concentrations. The avidities of several oligomeric mixtures were evaluated by means of a competitive binding assay using HEK293 cells engineered to overexpress the melanocortin 4 receptor. When based on total MSH4 concentrations, avidities were only minimally enhanced compared with a monovalent control. The lack of variation in the effect of ligands on probe binding is consistent with high off rates for MSH4 in both monovalent and oligomeric constructs relative to that of the competing probe.

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Section: Introductionmentioning

confidence: 99%

Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2 strategy

Dehigaspitiya

Suryakiran

Weber

et al. 2015

Tetrahedron Letters

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“…162,163 1,2,3-Triazoles possess two critical physicochemical similarities to the amide bonds that normally link amino acids: planarity and the ability to act as hydrogen bond acceptors. 163,164 Yet unlike amide bonds, triazoles are resistant to protease or peptidase metabolism in vivo.…”

Section: Emerging Applicationsmentioning

confidence: 99%

Click Chemistry and Radiochemistry: The First 10 Years

Meyer¹,

et al. 2016

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The advent of click chemistry has had a profound influence on almost all branches of chemical science. This is particularly true of radiochemistry and the synthesis of agents for positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted radiotherapy. The selectivity, ease, rapidity, and modularity of click ligations make them nearly ideally suited for the construction of radiotracers, a process that often involves working with biomolecules in aqueous conditions with inexorably decaying radioisotopes. In the following pages, our goal is to provide a broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry. The discussion will focus on four areas that we believe underscore the critical advantages provided by click chemistry: (i) the use of prosthetic groups for radiolabeling reactions, (ii) the creation of coordination scaffolds for radiometals, (iii) the site-specific radiolabeling of proteins and peptides, and (iv) the development of strategies for in vivo pretargeting. Particular emphasis will be placed on the four most prevalent click reactions—the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), the strainpromoted azide-alkyne cycloaddition (SPAAC), the inverse electron demand Diels-Alder reaction (IEDDA), and the Staudinger ligation—although less well-known click ligations will be discussed as well. Ultimately, it is our hope that this review will not only serve to educate readers but will also act as a springboard, inspiring synthetic chemists and radiochemists alike to harness click chemistry in even more innovative and ambitious ways as we embark upon the second decade of this fruitful collaboration.

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“…In this regard, various strategies have emerged for the synthesis of constrained cyclic peptides with different structural motifs emerging at the site of macrocyclization. Commonly applied strategies include disulfide or lactam bridge formation [53], ring-closing metathesis (RCM) [54], azido-alkyne cycloaddition [55], and palladium-catalyzed reactions [15,56,57]. Of specific importance to the current review are the biaryl-bridges, which gained interest for the stabilization of α-helices and β-sheets [58,59].…”

Section: Introductionmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

et al. 2017

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Abstract:The (site-selective) derivatization of amino acids and peptides represents an attractive field with potential applications in the establishment of structure-activity relationships and labeling of bioactive compounds. In this respect, bioorthogonal cross-coupling reactions provide valuable means for ready access to peptide analogues with diversified structure and function. Due to the complex and chiral nature of peptides, mild reaction conditions are preferred; hence, a suitable cross-coupling reaction is required for the chemical modification of these challenging substrates. The Suzuki reaction, involving organoboron species, is appropriate given the stability and environmentally benign nature of these reactants and their amenability to be applied in (partial) aqueous reaction conditions, an expected requirement upon the derivatization of peptides. Concerning the halogenated reaction partner, residues bearing halogen moieties can either be introduced directly as halogenated amino acids during solid-phase peptide synthesis (SPPS) or genetically encoded into larger proteins. A reversed approach building in boron in the peptidic backbone is also possible. Furthermore, based on this complementarity, cyclic peptides can be prepared by halogenation, and borylation of two amino acid side chains present within the same peptidic substrate. Here, the Suzuki-Miyaura reaction is a tool to induce the desired cyclization. In this review, we discuss diverse amino acid and peptide-based applications explored by means of this extremely versatile cross-coupling reaction. With the advent of peptide-based drugs, versatile bioorthogonal conversions on these substrates have become highly valuable.

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Peptide Conjugation via CuAAC ‘Click’ Chemistry

Cited by 94 publications

References 98 publications

Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2 strategy

Synthesis and bioactivity of MSH4 oligomers prepared by an A2+ B2 strategy

Click Chemistry and Radiochemistry: The First 10 Years

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

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