Chemo- and Regioselective Ethynylation of Tryptophan-Containing Peptides and Proteins.

Ethynylation of various tryptophan-containing peptides and a single model protein was achieved using Waser's reagent, 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1 H)-one (TIPS-EBX), under gold(I) catalysis. It was demonstrated by NMR that the ethynylation occurred selectively at the C2-position of the indole ring of tryptophan. Further, MS/MS showed that the tryptophan residues could be modified selectively with ethynyl functionalities even when the tryptophan was present as a part of the protein. Finally, the terminal alkyne was used to label a model peptide with a fluorophore by means of copper-catalyzed click chemistry.

[1]  J. V. Hest,et al.  Stimulus responsive peptide based materials. , 2010, Chemical Society reviews.

[2]  A. Heck,et al.  Metal-free and pH-controlled introduction of azides in proteins , 2011 .

[3]  Itaru Hamachi,et al.  Protein organic chemistry and applications for labeling and engineering in live-cell systems. , 2013, Angewandte Chemie.

[4]  Daniel B. Werz,et al.  Ethinylbenziodoxolon (EBX): Alkinübertragung in umgekehrter Weise , 2015 .

[5]  S. Buchwald,et al.  Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. , 2008, Accounts of chemical research.

[6]  J. Waser,et al.  Direct alkynylation of indole and pyrrole heterocycles. , 2009, Angewandte Chemie.

[7]  M. Francis,et al.  Selective tryptophan modification with rhodium carbenoids in aqueous solution. , 2004, Journal of the American Chemical Society.

[8]  F. Albericio,et al.  New peptide architectures through C–H activation stapling between tryptophan–phenylalanine/tyrosine residues , 2015, Nature Communications.

[9]  A. Adibekian,et al.  Proteome-Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents. , 2015, Angewandte Chemie.

[10]  U. Ribel,et al.  Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin , 2012, Pharmaceutical Research.

[11]  F. Carlsson.  The selective S-alkylation of a methionine residue in an elapid venom cardiotoxin. , 1987, The International journal of biochemistry.

[12]  M. Finn,et al.  Copper‐Catalyzed Azide–Alkyne Click Chemistry for Bioconjugation , 2011, Current protocols in chemical biology.

[13]  Luke G Green,et al.  A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. , 2002, Angewandte Chemie.

[14]  A. Pavlov,et al.  Selective ruthenium labeling of the tryptophan residue in the bee venom Peptide melittin. , 2015, Chemistry.

[15]  M. Ghadiri,et al.  Chemoselective Pd(0)-catalyzed peptide coupling in water. , 2001, Organic letters.

[16]  R. Liskamp,et al.  Synthesis of DOTA-conjugated multimeric [Tyr3]octreotide peptides via a combination of Cu(I)-catalyzed "click" cycloaddition and thio acid/sulfonyl azide "sulfo-click" amidation and their in vivo evaluation. , 2010, Journal of medicinal chemistry.

[17]  M. Francis,et al.  Tyrosine-selective protein alkylation using pi-allylpalladium complexes. , 2006, Journal of the American Chemical Society.

[18]  T. Deming,et al.  Reversible chemoselective tagging and functionalization of methionine containing peptides. , 2013, Chemical communications.

[19]  Franz P. Schmidtchen,et al.  Biokonjugation von Peptiden durch Palladium-katalysierte C-C-Kreuzkupplung in Wasser , 1998 .

[20]  F. Albericio,et al.  Postsynthetic modification of peptides: chemoselective C-arylation of tryptophan residues. , 2010, Chemistry.

[21]  B. Liedberg,et al.  Photo-induced conjugation of tetrazoles to modified and native proteins. , 2015, Organic & biomolecular chemistry.

[22]  J. Waser,et al.  C2-selective direct alkynylation of indoles. , 2013, Organic letters.

[23]  Douglas D Young,et al.  Development and Optimization of Glaser-Hay Bioconjugations. , 2015, Angewandte Chemie.

[24]  C. Barbas,et al.  Tyrosine bioconjugation through aqueous ene-type reactions: a click-like reaction for tyrosine. , 2010, Journal of the American Chemical Society.

[25]  F. Schmidtchen,et al.  Bioconjugation of Peptides by Palladium-Catalyzed C-C Cross-Coupling in Water. , 1998, Angewandte Chemie.

[26]  C. Barbas,et al.  Facile and stabile linkages through tyrosine: bioconjugation strategies with the tyrosine-click reaction. , 2013, Bioconjugate chemistry.

[27]  M. Wolfert,et al.  Protein Modification by Strain-Promoted Alkyne–Nitrone Cycloaddition , 2010, Angewandte Chemie.

[28]  A. Whitwood,et al.  A mild and selective Pd-mediated methodology for the synthesis of highly fluorescent 2-arylated tryptophans and tryptophan-containing peptides: a catalytic role for Pd(0) nanoparticles? , 2014, Chemical communications.

[29]  F. Veronese,et al.  Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase. , 2008, Advanced drug delivery reviews.

[30]  J. Waser,et al.  Gold-Catalyzed Alkynylation: Acetylene-Transfer instead of Functionalization , 2013 .

[31]  David J Brayden,et al.  Direct peptide bioconjugation/PEGylation at tyrosine with linear and branched polymeric diazonium salts. , 2012, Journal of the American Chemical Society.

[32]  M. Finn,et al.  Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation. , 2009, Angewandte Chemie.

[33]  Yousuke Takaoka,et al.  Organische Proteinchemie und ihre Anwendung für Markierungen und Engineering in Lebendzellsystemen , 2013 .

[34]  R. Scopelliti,et al.  Ethynyl benziodoxolones for the direct alkynylation of heterocycles: structural requirement, improved procedure for pyrroles, and insights into the mechanism. , 2012, Chemistry.

[35]  Morten Meldal,et al.  Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. , 2002, The Journal of organic chemistry.

[36]  K. Geoghegan,et al.  Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Application to modification at N-terminal serine. , 1992, Bioconjugate chemistry.

[37]  Z. Ball,et al.  Site-specific protein modification with a dirhodium metallopeptide catalyst. , 2011, ACS chemical biology.

[38]  H. Klok,et al.  Arginine-specific modification of proteins with polyethylene glycol. , 2011, Biomacromolecules.

[39]  M. Francis,et al.  Chemoselective tryptophan labeling with rhodium carbenoids at mild pH. , 2009, Journal of the American Chemical Society.

[40]  D. Werz,et al.  Ethynyl Benziodoxolone (EBX): Installing Alkynes the Reversed Way. , 2015, Angewandte Chemie.