The increasing popularity of peptides as promising molecular scaffolds for biomedical applications and as valuable biochemical probes makes new methods allowing for their modification highly desirable. We describe herein an optimized protocol based on a sequence of CuAAC click reactions and selective deprotection steps, which leads to an efficient multi-functionalization of synthetic peptides. The methodology has been successfully applied to the construction of defined heteroglycopeptides and fluorophore-quencher-containing probes for proteases. The developed chemistry thus represents an important addition to the available toolbox of methods enabling efficient postsynthetic modification of peptides. The commercial availability of numerous azide probes further greatly extends the application potential of the described methodology.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo nám 2 16610 Prague Czech Republic

Org Biomol Chem. 2018 Sep 19;16(36):6825. doi: 10.1039/c8ob90127a. PubMed

Zobrazit více v PubMed

Behrendt R., White P., Offer J. J. Pept. Sci. 2016;22:4–27. PubMed PMC

Fosgerau K., Hoffmann T. Drug Discovery Today. 2015;20:122–128. PubMed

Kaspar A. A., Reichert J. M. Drug Discovery Today. 2013;18:807–817. PubMed

Lau J. L., Dunn M. K. Bioorg. Med. Chem. 2018;26:2700–2707. PubMed

Rhodes C. A., Pei D. H. Chem. – Eur. J. 2017;23:12690–12703. PubMed PMC

Katz C., Levy-Beladev L., Rotem-Bamberger S., Rito T., Rudiger S. G. D., Friedler A. Chem. Soc. Rev. 2011;40:2131–2145. PubMed

Szymczak L. C., Kuo H. Y., Mrksich M. Anal. Chem. 2018;90:266–282. PubMed PMC

Jonker A. M., Löwik D. W. P. M., van Hest J. C. M. Chem. Mater. 2012;24:759–773.

Sawada T. and Serizawa T., in Advances in Bioinspired and Biomedical Materials Volume 1, American Chemical Society, 2017, ch. 3, vol. 1252, pp. 31–48.

van Hest J. C. M. Bioconjugate Chem. 2017;28:689–690.

deGruyter J. N., Malins L. R., Baran P. S. Biochemistry. 2017;56:3863–3873. PubMed PMC

Carrico I. S. Chem. Soc. Rev. 2008;37:1423–1431. PubMed

Hackenberger C. P., Schwarzer D. Angew. Chem., Int. Ed. 2008;47:10030–10074. PubMed

Basle E., Joubert N., Pucheault M. Chem. Biol. 2010;17:213–227. PubMed

Spicer C. D., Davis B. G. Nat. Commun. 2014;5:4740. PubMed

Boutureira O., Bernardes G. J. Chem. Rev. 2015;115:2174–2195. PubMed

Meldal M., Tornoe C. W. Chem. Rev. 2008;108:2952–3015. PubMed

Lallana E., Riguera R., Fernandez-Megia E. Angew. Chem., Int. Ed. 2011;50:8794–8804. PubMed

Haldon E., Nicasio M. C., Perez P. J. Org. Biomol. Chem. 2015;13:9528–9550. PubMed

Gramlich P. M., Warncke S., Gierlich J., Carell T. Angew. Chem., Int. Ed. 2008;47:3442–3444. PubMed

Hayashi G., Kamo N., Okamoto A. Chem. Commun. 2017;53:5918–5921. PubMed

Jan P., Benjamin F., Miloš B., Jan H., Mehdi A., Jiri J. Eur. J. Org. Chem. 2018 doi: 10.1002/ejoc.201800601. DOI

Valverde I. E., Delmas A. F., Aucagne V. Tetrahedron. 2009;65:7597–7602.

Meldal M. Curr. Opin. Struct. Biol. 1994;4:710–718.

Hironobu H., Yoshiaki N. Pept. Sci. 2007;88:308–324. PubMed

Worrell B. T., Malik J. A., Fokin V. V. Science. 2013;340:457–460. PubMed PMC

Inglis A. S., Edman P. Anal. Biochem. 1970;37:73–80. PubMed

Neefjes J., Dantuma N. P. Nat. Rev. Drug Discovery. 2004;3:58. PubMed PMC

Sivakumar K., Xie F., Cash B. M., Long S., Barnhill H. N., Wang Q. Org. Lett. 2004;6:4603–4606. PubMed