Solid phase click chemistry

Solid-phase click chemistry in organic solvents (e.g., DMF and THF) works well, seemingly independent of the support Resins such as polystyrene and polyethylene glycol (PEGA) attest to tolerance to both nonpolar and polar types. As outlined in the original Meldal el al. papers, novel triazole-containing polypeptides... 

Solid phase click chemistry. General procedure to peptidotriazoleP ... 

In another application of coupling proteins to surfaces using click chemistry, Duckworth et al. (2006) carried out prenylation of a protein using a farnesyl azide derivative and the enzyme farnesyl transferase for subsequent chemoselective ligation to alkyne-functionalized agarose beads. The result is a highly discrete, site-specific attachment of the protein to the solid phase at a single location. 

Jolck RL Berg RH, Andresen TL (2010) Solid-phase synthesis of PEGylated lipopeptides using click chemistry. Bioconjugate Chem 21 807-810... 

The availabiUty of functionalized 2(lH)-pyrazinone in combination with the use of microwave accelerated solid-phase chemistry constitutes a soUd foundation for generating large libraries of compoimds suitable for medicinal chemistry. The authors have also shown that the scaffold can be further functionalized using the principles of click-chemistry , thereby paving the way towards highly substituted 2-pyridone structures [45-47]. 

Another inventive extension of click chemistry is the concept of cUck-resins that promote solid phase supported reactions to work under nearly perfect conditions, fulfilling the requirements of click chemistry [32, 33]. This approach has enabled the assembly of a library of carboxylic arene bioisoesters, with the general formula V [34] as potential dopamine D4 receptor ligands [35]. In essence, the authors completed parallel synthesis of bioactive tert-amines V, utilizing triazolyl-methylacrylate 7 as a linker. The product was readily generated from the commercial azidomethyl substituted polystyrene 5 and propargyl acrylate 6 via Cu(I) catalyzed 1,3-dipolar cycloaddition (Scheme 15.4). 

There are four different chemical reactions that have been used to crosslink polymers with peptide sequences (Fig. 6.8) (i) amide bond formation (ii) Michael-type addition (iii) Huisgen cycloaddition (click reaction) and (iv) radical polymerisation. The amide bond formation follows typical solid phase peptide synthesis (SPPS) protocols and does not require functionalisation of the termini of the peptide sequence. Fluorenyhnethoxycarbonyl (Fmoc) protection of the N-terminus allows attachment of the peptide sequence to an amine-bearing polymer. After removal of the Fmoc group, the amine-terminated peptide-polymer conjugate can be reacted with a second polymer bearing carboxylic acid functionalities using the same coupling chemistry (Maier et al, 2011). For Michael-type additions the peptide... 

The solid-phase synthesis of adenyl-peptide conjugates was described by Filippov et al. utilizing click chemistry to attach the azide-derived 2-alkoxy-8-hydroxy adenine 63 to a major histocompatibility complex (MHC) class 1 epitope. Fmoc-chemistry was used to assemble the alkyne-conjugated peptide followed by CuAAC with 63 and it was shown that one of the adenyl peptide conjugates could enhance the T-cell response compared to a mixture of 63 and the unmodified peptide (see Scheme 10.19). 

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