On-resin multicomponent protocols for biopolymer assembly and derivatization

Daniel G. Rivera, Manuel G. Ricardo, Aldrin V. Vasco, Ludger A. Wessjohann, Erik V. Van der Eycken

Published: 2021-01-19 DOI: 10.1038/s41596-020-00445-6

Solid-phase synthesis

Multicomponent reactions

Biopolymer assembly

Derivatization

Peptide modification

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Supplementary information

Reporting Summary

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The eINTACT method for studying nuclear changes in host plant cells targeted by bacterial effectors in native infection contexts

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Supplementary information

Merrifield, R. B. Automated synthesis of peptides. Science 150, 178–185 (1965).
Plante, O. J., Palmacci, E. R. & Seeberger, P. H. Automated solid-phase synthesis of oligosaccharides. Science 291, 1523–1527 (2001).
Caruthers, M. Gene synthesis machines: DNA chemistry and its uses. Science 230, 281–285 (1985).
Scaringe, S. A., Wincott, F. E. & Caruthers, M. H. Novel RNA synthesis method using 5′-O-silyl-2′-O-orthoester protecting groups. J. Am. Chem. Soc. 120, 11820–11821 (1998).
Mäde, V., Els-Heindl, S. & Beck-Sickinger, A. G. Automated solid-phase peptide synthesis to obtain therapeutic peptides. Beilstein J. Org. Chem. 10, 1197–1212 (2014).
Kröck, L. et al. Streamlined access to conjugation-ready glycans by automated synthesis. Chem. Sci. 3, 1617–1622 (2012).
Seeberger, P. H. & Werz, D. B. Synthesis and medical applications of oligosaccharides. Nature 446, 1046–1051 (2007).
Lashkari, D. A., Hunicke-Smith, S. P., Norgren, R. M., Davis, R. W. & Brennan, T. An automated multiplex oligonucleotide synthesizer: development of high-throughput, low-cost DNA synthesis. Proc. Natl Acad. Sci. USA 92, 7912–7915 (1995).
Seeberger, P. H. Automated oligosaccharide synthesis. Chem. Soc. Rev. 37, 19–28 (2008).
Dömling, A. & Ugi, I. Multicomponent reactions with isocyanides. Angew. Chem. Int. Ed. 39, 3168–3210 (2000).
Zhu, J., Qian, W. & Mei-Xiang, W. Multicomponent Reactions in Organic Synthesis (Wiley, 2015).
Ruijter, E., Scheffelaar, R. & Orru, R. V. A. Multicomponent reaction design in the quest for molecular complexity and diversity. Angew. Chem. Int. Ed. 50, 6234–6246 (2011).
Brauch, S., van Berkel, S. S. & Westermann, B. Higher-order multicomponent reactions: beyond four reactants. Chem. Soc. Rev. 42, 4948–4962 (2013).
Toure, B. B. & Hall, D. G. Natural product synthesis using multicomponent reaction strategies. Chem. Rev. 109, 4439–4486 (2009).
Kreye, O., Tóth, T. & Meier, M. A. R. Introducing multicomponent reactions to polymer science: Passerini reactions of renewable monomers. J. Am. Chem. Soc. 133, 1790–1792 (2011).
Reguera, L., Méndez, Y., Humpierre, A. R., Valdés, O. & Rivera, D. G. Multicomponent reactions in ligation and bioconjugation chemistry. Acc. Chem. Res. 51, 1475–1486 (2018).
Dömling, A., Wang, W. & Wang, K. Chemistry and biology of multicomponent reactions. Chem. Rev. 112, 3083–3135 (2012).
Slobbe, P., Ruijter, E. & Orru, R. V. A. Recent applications of multicomponent reactions in medicinal chemistry. Med. Chem. Commun 3, 1189–1218 (2012).
Dax, S. L., McNally, J. J. & Youngman, M. A. Multi-component methodologies in solid-phase organic synthesis. Curr. Med. Chem. 6, 255–270 (1999).
Banfi, L., Guanti, G., Riva, R. & Basso, A. Multicomponent reactions in solid-phase synthesis. Curr. Opin. Drug Discov. Dev. 10, 704–714 (2007).
Reguera, L. & Rivera, D. G. Multicomponent reaction toolbox for peptide macrocyclization and stapling. Chem. Rev. 119, 9836–9860 (2019).
Ugi, I. Versuche mit Isonitrilen. Angew. Chem. Int. Ed. 71, 386–386 (1959).
Paserini, M. & Simone, L. Sopra gli isonitrili (I). Composto del p-isonitril-azobenzolo con acetone ed acido acetico. Gazz. Chim. Ital. 51, 126–129 (1921).
Petasis, N. A. & Akrltopoulou, I. The boronic acid Mannich reaction: a new method for the synthesis of geometrically pure allylamines. Tetrahedron Lett. 34, 583–586 (1993).
Isidro-Llobet, A., Álvarez, M. & Albericio, F. Amino acid-protecting groups. Chem. Rev. 109, 2455–2504 (2009).
Banfi, L. & Riva, R. The Passerini reaction. Org. React 65, 1–140 (2005).
Chatterjee, J., Rechenmacher, F. & Kessler, H. N-methylation of peptides and proteins: an important element for modulating biological functions. Angew. Chem. Int. Ed. 52, 254–269 (2013).
Morales, F. E. et al. Aminocatalysis-mediated on-resin Ugi reactions: application in the solid-phase synthesis of N-substituted and tetrazolo lipopeptides and peptidosteroids. Org. Lett. 17, 2728–2731 (2015).
Alsina, J. & Albericio, F. Solid-phase synthesis of C-terminal modified peptides. Biopolymers 71, 454–477 (2003).
Fernández-Llamazares, A. I., Spengler, J. & Albericio, F. Review rackbone N-modified peptides: how to meet the challenge of secondary amine acylation. Pept. Sci. 104, 435–452 (2015).
Palomo, J. M. Solid-phase peptide synthesis: an overview focused on the preparation of biologically relevant peptides. RSC Adv. 4, 32658–32672 (2014).
Puentes, A. R., Morejón, M. C., Rivera, D. G. & Wessjohann, L. A. Peptide macrocyclization assisted by traceless turn inducers derived from Ugi peptide ligation with cleavable and resin-linked amines. Org. Lett. 19, 4022–4025 (2017).
Morejón, M. C., Laub, A., Westermann, B., Rivera, D. G. & Wessjohann, L. A. Solution-and solid-phase macrocyclization of peptides by the Ugi–Smiles multicomponent reaction: synthesis of N-aryl-bridged cyclic lipopeptides. Org. Lett. 18, 4096–4099 (2016).
Vasco, A. V. et al. A multicomponent stapling approach to exocyclic functionalized helical peptides: adding lipids, sugars, PEGs, labels, and handles to the lactam bridge. Bioconjug. Chem. 30, 253–259 (2019).
Vasco, A. V. et al. Synthesis of lactam-bridged and lipidated cyclo-peptides as promising anti-phytopathogenic agents. Molecules 25, 811 (2020).
Hili, R., Rai, V. & Yudin, A. K. Macrocyclization of linear peptides enabled by amphoteric molecules. J. Am. Chem. Soc. 132, 2889–2891 (2010).
Treder, A. P. et al. Solid-phase parallel synthesis of functionalised medium-to-large cyclic peptidomimetics through three-component coupling driven by aziridine aldehyde dimers. Chem. Eur. J. 21, 9249–9255 (2015).
Bucci, R. et al. On-resin multicomponent 1,3-dipolar cycloaddition of cyclopentanone–proline enamines and sulfonylazides as an efficient tool for the synthesis of amidino depsipeptide mimics. Amino Acids 52, 15–24 (2020).
Jad, Y. E., Gudimella, S. K., Govender, T., de la Torre, B. G. & Albericio, F. Solid-phase synthesis of pyrrole derivatives through a multicomponent reaction involving Lys-containing peptides. ACS Comb. Sci. 20, 187–191 (2018).
Estevez, V., Villacampa, M. & Menéndez, J. C. Multicomponent reactions for the synthesis of pyrroles. Chem. Soc. Rev. 39, 4402–4421 (2010).
Petasis, N. A. & Zavialov, I. A. A new and practical synthesis of α-amino acids from alkenyl boronic acids. J. Am. Chem. Soc. 119, 445–446 (1997).
Ricardo, M. G., LLanes, D., Wessjohann, L. A. & Rivera, D. G. Introducing the Petasis reaction for the late-stage multicomponent diversification, labeling and stapling of peptides. Angew. Chem. Int. Ed. 58, 2700–2704 (2019).
Cornier, P. G., Delpiccolo, C. M. L., Boggián, D. B. & Mata, E. G. Solid-phase Petasis multicomponent reaction for the generation of β-lactams 3-substituted with non-proteinogenic α-amino acids. Tetrahedron Lett. 54, 4742–4745 (2013).
Candeias, N. R., Montalbano, F., Cal, P. M. S. D. & Gois, P. M. P. Boronic acids and esters in the Petasis-borono Mannich multicomponent reaction. Chem. Rev. 110, 6169–6193 (2010).
Yamaguchi, A., Kaldas, S. J., Appavoo, S. D., Diaz, D. B. & Yudin, A. K. Conformationally stable peptide macrocycles assembled using the Petasis borono-Mannich reaction. Chem. Commun. 55, 10567–10570 (2019).
Zhang, J., Proulx, C., Tomberg, A. & Lubell, W. D. Multicomponent diversity-oriented synthesis of aza-lysine-peptide mimics. Org. Lett. 16, 298–301 (2013).
Peshkov, V. A., Pereshivko, O. P. & Van der Eycken, E. V. A walk around the A3-coupling. Chem. Soc. Rev. 41, 3790–3807 (2012).
Hansen, J., Diness, F. & Meldal, M. C-Terminally modified peptides via cleavage of the HMBA linker by O-, N- or S-nucleophiles. Org. Biomol. Chem. 14, 3238–3245 (2016).
So, W. H. & Xia, J. On-resin Passerini reaction toward C‑terminal photocaged peptides. Org. Lett. 22, 214–218 (2020).
Szymannski, W., Velema, W. A. & Feringa, B. L. Photocaging of carboxylic acids: a modular approach. Angew. Chem. Int. Ed. 53, 8682–8686 (2014).
Constabel, F. & Ugi, I. Repetitive Ugi reactions. Tetrahedron 57, 5785–5789 (2001).
Pando, O. et al. The multiple multicomponent approach to natural product mimics: tubugis, N-substituted anticancer peptides with picomolar activity. J. Am. Chem. Soc. 133, 7692–7695 (2011).
Wessjohann, L. A., Neves Filho, R. A.W. & Rivera, D. G. in Isocyanide Chemistry—Applications in Synthesis and Materials Science (ed. Nenajdenko, V. G.) 233–262 (Wiley, 2012).
Jobin, S. et al. Toward solid-phase peptide fragment ligation by a traceless-Ugi multicomponent reaction approach. Org. Biomol. Chem. 14, 11230–11237 (2016).
Dawson, P., Muir, T., Clark-Lewis, I. & Kent, S. Synthesis of proteins by native chemical ligation. Science 266, 776–779 (1994).
Pusterla, I. & Bode, J. W. An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations. Nat. Chem. 7, 668–672 (2015).
Saxon, E., Armstrong, J. I. & Bertozzi, C. R. A “traceless” Staudinger ligation for the chemoselective synthesis of amide bonds. Org. Lett. 2, 2141–2143 (2000).
Jensen, K. J. et al. Peptides—Chemistry, Structure and Biology: Proceedings of the Fourteenth American Peptide Symposium (eds Kaumaya, P. T. P. & Hodges, R. S.) 30–32 (Mayflower Scientific, 1996).
Jovin, S., Beaumont, C. & Biron, E. Development of a solid-phase traceless-Ugi multicomponent reaction for backbone anchoring and cyclic peptide synthesis. Pept. Sci. 111, e24044 (2018).
Ricardo, M. G., Marrero, J. F., Valdéz, O., Rivera, D. G. & Wessjohann, L. A. Peptide backbone stapling strategy enabled by the multicomponent incorporation of amide N-substituents. Chem. Eur. J. 25, 769–774 (2019).
Ricardo, M. G. et al. Improved stability and tunable functionalization of parallel β-sheets via multicomponent N-alkylation of the turn moiety. Angew. Chem Int. Ed. 59, 259–263 (2020).
Patgiri, A., A. L. Jochim, A. L. & Arora, P. S. A hydrogen bond surrogate approach for stabilization of short peptide sequences in α-helical conformation. Acc. Chem. Res. 41, 1289–1300 (2008).
Ricardo, M. G., Vasco, A. V., Rivera, D. G. & Wessjohann, L. A. Stabilization of cyclic β-hairpins by Ugi reaction-derived N-alkylated peptides: the quest for functionalized β-turns. Org. Lett. 21, 7307–7310 (2019).
Patch, J. A., Kirshenbaum, K., Seurynck, S. L., Zuckermann, R. N. & Barron, A. E. Pseudo-Peptides in Drug Discovery (ed. Nielsen, P. E.) 1–30 (Wiley, 2004).
Yoo, B. & Kirshenbaum, K. Peptoid architectures: elaboration, actuation, and application. Curr. Opin. Chem. Biol. 12, 714–721 (2008).
Kodadek, T. & McEnaney, P. J. Towards vast libraries of scaffold-diverse, conformationally constrained oligomers. Chem. Commun. 52, 6038–6059 (2016).
Conradi, R. A., Hilgers, A. R., Ho, N. F. H. & Burton, P. S. The influence of peptide structure on transport across Caco-2 cells. II. Peptide bond modification which results in improved permeability. Pharm. Res. 9, 435–439 (1992).
Miller, S. M. et al. Proteolytic studies of homologous peptide and N-substituted glycine peptoid oligomers. Bioorg. Med. Chem. Lett. 4, 2657–2662 (1994).
Pels, K. & Kodadek, T. Solid-phase synthesis of diverse peptide tertiary amides by reductive amination. ACS Comb. Sci. 17, 152–155 (2015).
Rivera, D. G. et al. A multiple multicomponent approach to chimeric peptide–peptoid podands. Chem. Eur. J. 19, 6417–6428 (2013).
Zhang, X. et al. Ugi reaction of natural amino acids: a general route toward facile synthesis of polypeptoids for bioapplications. ACS Macro Lett. 5, 1049–1054 (2016).
Vercillo, O. E., Andrade, C. K. Z. & Wessjohann, L. A. Design and synthesis of cyclic RGD pentapeptoids by consecutive Ugi reactions. Org. Lett. 10, 205–208 (2008).
Wessjohann, L. A., Phuong, T. T. & Westermann, B. Method for producing condensation products from N-substituted glycine derivatives by sequential Ugi-multicomponent reactions for use as pharmaceutical substances. PTC International Patent Application 2008022800. Chem. Abstr. 148, 285479 (2008).
Hartweg, M. et al. Ugi multicomponent reaction to prepare peptide-peptoid hybrid structures with diverse chemical functionalities. Polym. Chem. 9, 482–489 (2018).
Dömling, A., Chi, K. Z. & Barrere, M. A novel method to highly versatile monomeric PNA building blocks by multi component reactions. Bioorg. Med. Chem. Lett. 9, 2871–2874 (1999).
Maison, W., Schlemminger, I., Westerhoff, O. & Martens, J. Multicomponent synthesis of novel amino acid-nucleobase chimeras: a versatile approach to PNA-monomers. Bioorg. Med. Chem. 8, 1343–1360 (2000).
Xu, P. et al. Synthesis of PNA monomers and dimers by Ugi four-component reaction. Synthesis 8, 1171–1176 (2003).
Saarbach, J., Masi, D., Zambaldo, C. & Winssinger, N. Facile access to modified and functionalized PNAs through Ugi-based solid phase oligomerization. Bioorg. Med. Chem. 25, 5171–5177 (2017).
Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 254, 1497–1500 (1991).
Brenner, S. & Lerner, R. A. Encoded combinatorial chemistry. Proc. Natl Acad. Sci. USA 89, 5381–5383 (1992).
Dickson, P. & Kodadek, T. Chemical composition of DNA-encoded libraries, past present and future. Org. Biomol. Chem. 17, 4676–4688 (2019).
Potowski, M. et al. Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions. Chem. Sci. 10, 10481–10492 (2019).
Potowski, M., Kunig, V. B. K., Losch, F. & Brunschweiger, A. Synthesis of DNA-coupled isoquinolones and pyrrolidines by solid phase ytterbium- and silver-mediated imine chemistry. Med. Chem. Commun 10, 1082–1093 (2019).
Kunig, V. B. K., Ehrt, C., Dömling, A. & Brunschweiger, A. Isocyanide multicomponent reactions on solid-phase-coupled DNA oligonucleotides for encoded library synthesis. Org. Lett. 21, 7238–7243 (2019).
Potowski, M., Esken, R. & Brunschweiger, A. Translation of the copper/bipyridine-promoted Petasis reaction to solid-phase coupled DNA for encoded library synthesis. Bioorg. Med. Chem. 28, 115441–115448 (2020).
Ghashghaei, O., Masdeu, C., Alonso, C., Palacios, F. & Lavilla, R. Recent advances of the Povarov reaction in medicinal chemistry. Drug Discov. Today Technol. 29, 71–79 (2018).
Kunig, V. B. K. et al. TEAD–YAP interaction inhibitors and MDM2 binders from DNA-encoded indole-focused Ugi peptidomimetics. Angew. Chem. Int. Ed. 59, 20338–20342 (2020).
Volkmer, R. Synthesis and application of peptide arrays: quo vadis SPOT technology. ChemBioChem 10, 1431–1442 (2009).
Lin, Q. & Blackwell, H. E. Rapid synthesis of diketopiperazine macroarrays via Ugi four-component reactions on planar solid supports. Chem. Commun. 27, 2884–2886 (2006).
Ridder, B., Mattes, D. S., Nesterov-Mueller, A., Breitling, F. & Meier, M. A. R. Peptide array functionalization via the Ugi four-component reaction. Chem. Commun. 53, 5553–5556 (2017).
Khan, M. et al. Recent advances in multicomponent reactions involving carbohydrates. RSC Adv. 5, 57883–57905 (2015).
de Nooy, A. E. J., Masci, G. & Crescenzi, V. Versatile synthesis of polysaccharide hydrogels using the Passerini and Ugi multicomponent condensations. Macromolecules 32, 1318–1320 (1999).
Méndez, Y. et al. Multicomponent polysaccharide–protein bioconjugation in the development of antibacterial glycoconjugate vaccine candidates. Chem. Sci. 9, 2581–2588 (2018).
Hauck, N. et al. Droplet-assisted microfluidic fabrication and characterization of multifunctional polysaccharide microgels formed by multicomponent reactions. Polymers 10, 1055 (2018).
Shulepov, I. D., Kozhikhova, K. V., Panfilova, Y. S., Ivantsova, M. N. & Mironov, M. A. One-pot synthesis of cross-linked sub-micron microgels from pure cellulose via the Ugi reaction and their application as emulsifiers. Cellulose 23, 2549–2559 (2016).
Afshari, R. & Shaabani, A. Materials functionalization with multicomponent reactions: state of the art. ACS Comb. Sci. 20, 499–528 (2018).
Humpierre, A. R., et al. Expanding the scope of Ugi multicomponent bioconjugation to produce pneumococcal multivalent glycoconjugates as vaccine candidates Bioconjugate Chem. 31, 2231–2240 (2020)
Kaiser, E., Colescott, R. L., Bossinger, C. D. & Cook, P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal. Biochem. 34, 595–598 (1970).
Bayer, E. Towards the chemical synthesis of proteins. Angew. Chem. Int. Ed. 30, 113–129 (1991).
Meldal, M. Pega: a flow stable polyethylene glycol dimethyl acrylamide copolymer for solid phase synthesis. Tetrahedron Lett. 33, 3077–3080 (1992).
García-Martín, F. et al. ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides. J. Comb. Chem. 8, 213–220 (2006).

On-resin multicomponent protocols for biopolymer assembly and derivatization

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