Going Round in Circles with N→S Acyl Transfer

Abstract

It is not highly sophisticated, yet the N→S acyl transfer reaction of a native peptide sequence potentially fills an important technology gap. While several routes to synthetic peptide thioesters exist, only one is routinely applicable for biologically derived samples. Using the naturally occurring amino acid cysteine as the sole activator for N→S acyl transfer we have demonstrated transformation of synthetic and biologically derived precursors into thioesters for use in Native Chemical Ligation, providing a viable alternative for biological samples. Further refinement will be key to realising the full potential of this intriguing process, and increase the number of applications in peptide engineering and therapeutics.

1 Introduction

2 N→S acyl transfer in ‘normal’ peptide sequences

3 Reduced reactivity of internal Xaa-Cys motifs as an advantage in head-to-tail peptide cyclisation

4 Reduced reactivity of internal Xaa-Cys motifs as an advantage in modification and cyclisation of biologically produced precursors

5 Hydrazinolysis of Xaa-Cys motifs and the acyl hydrazide as a stable thioester equivalent

6 Rapid thioester formation via an N→Se acyl shift

7 Outlook and conclusions

Key words

thioester - native chemical ligation - cyclic peptides - acyl transfer

• References

• 1a de Duve C. Am. Sci. 1995; 83: 428
• 1b Bracher PJ. Snyder PW. Bohall BR. Whitesides GM. Origins Life Evol. Biospheres 2011; 41: 399
• 2 Dawson P. Muir T. Clark-Lewis I. Kent S. Science 1994; 266: 776
• 3 Wieland T. Bokelmann E. Bauer L. Lang HU. Lau H. Justus Liebigs Ann. Chem. 1953; 583: 129
• 4 Merrifield RB. J. Am. Chem. Soc. 1963; 85: 2149
• 5 Kent SB. H. Chem. Soc. Rev. 2009; 38: 338
• 6 Martin RB. Lowey S. Elson EL. Edsall JT. J. Am. Chem. Soc. 1959; 81: 5089
• 7 Shah NH. Muir TW. Chem. Sci. 2014; 5: 446
• 8 Zanotti G. Pinnen F. Lucente G. Tetrahedron Lett. 1985; 26: 5481
• 9 Kawakami T. Sumida M. Nakamura K. i. Vorherr T. Aimoto S. Tetrahedron Lett. 2005; 46: 8805
• 10 Nakamura K. i. Sumida M. Kawakami T. Vorherr T. Aimoto S. Bull. Chem. Soc. Jpn. 2006; 79: 1773
• 11 Ollivier N. Behr J.-B. El-Mahdi O. Blanpain A. Melnyk O. Org. Lett. 2005; 7: 2647
• 12 Ohta Y. Itoh S. Shigenaga A. Shintaku S. Fujii N. Otaka A. Org. Lett. 2006; 8: 467
• 13a Eryilmaz E. Shah NH. Muir TW. Cowburn D. J. Biol. Chem. 2014; 289: 14506
• 13b Mills KV. Johnson MA. Perler FB. J. Biol. Chem. 2014; 289: 14498
• 13c Liu Z. Frutos S. Bick MJ. Vila-Perelló M. Debelouchina GT. Darst SA. Muir TW. Proc. Natl. Acad. Sci. USA 2014; 111: 8422
• 13d Volkmann G. Mootz H. Cell. Mol. Life Sci. 2013; 70: 1185
• 14a Romanelli A. Shekhtman A. Cowburn D. Muir TW. Proc. Natl. Acad. Sci. USA 2004; 101: 6397
• 14b Callahan BP. Topilina NI. Stanger MJ. Van Roey P. Belfort M. Nat. Struct. Mol. Biol. 2011; 18: 630
• 15 Binschik J. Mootz HD. Angew. Chem. Int. Ed. 2013; 52: 4260
• 16a Kent S. Pept. Sci. 2010; 94: iv-ix
• 16b Kent SB. H. J. Pept. Sci. 2015; 21: 136
• 17a Zheng J.-S. Tang S. Huang Y.-C. Liu L. Acc. Chem. Res. 2013; 46: 2475
• 17b Ling JJ. Policarpo RL. Rabideau AE. Liao X. Pentelute BL. J. Am. Chem. Soc. 2012; 134: 10749
• 17c Unverzagt C. Kajihara Y. Chem. Soc. Rev. 2013; 42: 4408
• 17d Schnölzer M. Alewood P. Jones A. Alewood D. Kent S. Int. J. Pept. Res. Ther. 2007; 13: 31
• 18 Mende F. Seitz O. Angew. Chem. Int. Ed. 2011; 50: 1232
• 19 Melnyk O. Agouridas V. Curr. Opin. Chem. Biol. 2014; 22: 137
• 20 Bondalapati S. Jbara M. Brik A. Nat. Chem. 2016; 8: 407
• 21a Lee J. Kwon Y. Pentelute BL. Bang D. Bioconjugate Chem. 2011; 22: 1645
• 21b Bang D. Pentelute BL. Kent SB. H. Angew. Chem. Int. Ed. 2006; 45: 3985
• 22 Bang D. Kent SB. H. Angew. Chem. Int. Ed. 2004; 43: 2534
• 23 Li J. Li Y. He Q. Li Y. Li H. Liu L. Org. Biomol. Chem. 2014; 12: 5435
• 24a Thompson RE. Liu X. Alonso-García N. Pereira PJ. B. Jolliffe KA. Payne RJ. J. Am. Chem. Soc. 2014; 136: 8161
• 24b Moyal T. Hemantha HP. Siman P. Refua M. Brik A. Chem. Sci. 2013; 4: 2496
• 25 Malins LR. Payne RJ. Curr. Opin. Chem. Biol. 2014; 22: 70
• 26a Kan C. Danishefsky SJ. Tetrahedron 2009; 65: 9047
• 26b Wan Q. Danishefsky SJ. Angew. Chem. Int. Ed. 2007; 46: 9248
• 26c Yan LZ. Dawson PE. J. Am. Chem. Soc. 2001; 123: 526
• 27 Offer J. Pept. Sci. 2010; 94: 530
• 28 Ackrill T. Anderson DW. Macmillan D. Pept. Sci. 2010; 94: 495
• 29 Wu B. Chen J. Warren JD. Chen G. Hua Z. Danishefsky SJ. Angew. Chem. Int. Ed. 2006; 45: 4116
• 30 Loibl SF. Harpaz Z. Seitz O. Angew. Chem. Int. Ed. 2015; 54: 15055
• 31 Johnson EC. B. Kent SB. H. J. Am. Chem. Soc. 2006; 128: 6640
• 32 Xu M.-Q. Evans JrT. C. Methods 2001; 24: 257
• 33a Aimoto S. Pept. Sci. 1999; 51: 247
• 33b Hackeng TM. Griffin JH. Dawson PE. Proc. Natl. Acad. Sci. USA 1999; 96: 10068
• 34a Raz R. Burlina F. Ismail M. Downward J. Li J. Smerdon SJ. Quibell M. White PD. Offer J. Angew. Chem. Int. Ed. 2016; 55: 13174
• 34b Gates ZP. Dhayalan B. Kent SB. H. Chem. Commun. 2016; 52: 13979
• 35 Behrendt R. White P. Offer J. J. Pept. Sci. 2016; 22: 4
• 36a Clippingdale AB. Barrow CJ. Wade JD. J. Pept. Sci. 2000; 6: 225
• 36b Hasegawa K. Sha YL. Bang JK. Kawakami T. Akaji K. Aimoto S. Lett. Pept. Sci. 2001; 8: 277
• 36c Raz R. Rademann J. Org. Lett. 2011; 13: 1606
• 37 Blanco-Canosa JB. Dawson PE. Angew. Chem. Int. Ed. 2008; 47: 6851
• 38 Shin Y. Winans KA. Backes BJ. Kent SB. H. Ellman JA. Bertozzi CR. J. Am. Chem. Soc. 1999; 121: 11684
• 39a Mezzato S. Schaffrath M. Unverzagt C. Angew. Chem. Int. Ed. 2005; 44: 1650
• 39b Burlina F. Morris C. Behrendt R. White P. Offer J. Chem. Commun. 2012; 48: 2579
• 40 Kawakami T. Aimoto S. Tetrahedron 2009; 65: 3871
• 41 Nagaike F. Onuma Y. Kanazawa C. Hojo H. Ueki A. Nakahara Y. Nakahara Y. Org. Lett. 2006; 8: 4465
• 42 Kang J. Richardson JP. Macmillan D. Chem. Commun. 2009; 407
• 43 Kang J. Reynolds NL. Tyrrell C. Dorin JR. Macmillan D. Org. Biomol. Chem. 2009; 7: 4918
• 44 Richardson JP. Chan C.-H. Blanc J. Saadi M. Macmillan D. Org. Biomol. Chem. 2010; 8: 1351
• 45 Cowper B. Shariff L. Chen W. Gibson SM. Di W.-L. Macmillan D. Org. Biomol. Chem. 2015; 13: 7469
• 46 Asahina Y. Nabeshima K. Hojo H. Tetrahedron Lett. 2015; 56: 1370
• 47 Premdjee B. Adams AL. Macmillan D. Bioorg. Med. Chem. Lett. 2011; 21: 4973
• 48 Masania J. Li J. Smerdon SJ. Macmillan D. Org. Biomol. Chem. 2010; 8: 5113
• 49 Macmillan D. De Cecco M. Reynolds NL. Santos LF. A. Barran PE. Dorin JR. ChemBioChem 2011; 12: 2133
• 50 Adams AL. Cowper B. Morgan RE. Premdjee B. Caddick S. Macmillan D. Angew. Chem. Int. Ed. 2013; 52: 13062
• 51 Northfield SE. Wang CK. Schroeder CI. Durek T. Kan M.-W. Swedberg JE. Craik DJ. Eur. J. Med. Chem. 2014; 77: 248
• 52a Bhardwaj G. Mulligan VK. Bahl CD. Gilmore JM. Harvey PJ. Cheneval O. Buchko GW. Pulavarti SV. S. R. K. Kaas Q. Eletsky A. Huang P.-S. Johnsen WA. Greisen PJr. Rocklin GJ. Song Y. Linsky TW. Watkins A. Rettie SA. Xu X. Carter LP. Bonneau R. Olson JM. Coutsias E. Correnti CE. Szyperski T. Craik DJ. Baker D. Nature 2016; 538: 329
• 52b Clark RJ. Daly NL. Craik DJ. Biochem. J. 2006; 394: 85
• 52c Poth AG. Chan LY. Craik DJ. Pept. Sci. 2013; 100: 480
• 53a Tavassoli A. Benkovic SJ. Nat. Protoc. 2007; 2: 1126
• 53b Tarasava K. Freisinger E. Protein Eng., Des. Sel. 2014; 27: 481
• 53c Aboye TL. Camarero JA. J. Biol. Chem. 2012; 287: 27026
• 54a Nguyen GK. T. Wang S. Qiu Y. Hemu X. Lian Y. Tam JP. Nat. Chem. Biol. 2014; 10: 732
• 54b Nguyen GK. T. Qiu Y. Cao Y. Hemu X. Liu C.-F. Tam JP. Nat. Protoc. 2016; 11: 1977
• 54c Harris KS. Durek T. Kaas Q. Poth AG. Gilding EK. Conlan BF. Saska I. Daly NL. van der Weerden NL. Craik DJ. Anderson MA. Nat. Commun. 2015; 6: 10199
• 55a Wu Z. Guo X. Guo Z. Chem. Commun. 2011; 47: 9218
• 55b Antos JM. Popp MW.-L. Ernst R. Chew G.-L. Spooner E. Ploegh HL. J. Biol. Chem. 2009; 284: 16028
• 55c Jia X. Kwon S. Wang C.-IA. Huang Y.-H. Chan LY. Tan CC. Rosengren KJ. Mulvenna JP. Schroeder CI. Craik DJ. J. Biol. Chem. 2014; 289: 6627
• 56 Jagadish K. Gould A. Borra R. Majumder S. Mushtaq Z. Shekhtman A. Camarero JA. Angew. Chem. Int. Ed. 2015; 54: 8390
• 57 Tam JP. Wong CT. T. J. Biol. Chem. 2012; 287: 27020
• 58 Chen W. Kinsler VA. Macmillan D. Di W.-L. PLOS ONE 2016; 11: e0166268
• 59a Xie J. Schultz PG. Nat. Rev. Mol. Cell Biol. 2006; 7: 775
• 59b Davis L. Chin JW. Nat. Rev. Mol. Cell Biol. 2012; 13: 168
• 60a Fang G.-M. Li Y.-M. Shen F. Huang Y.-C. Li J.-B. Lin Y. Cui H.-K. Liu L. Angew. Chem. Int. Ed. 2011; 50: 7645
• 60b Wang P. Layfield R. Landon M. Mayer RJ. Ramage R. Tetrahedron Lett. 1998; 39: 8711
• 61a Reif A. Siebenhaar S. Tröster A. Schmälzlein M. Lechner C. Velisetty P. Gottwald K. Pöhner C. Boos I. Schubert V. Rose-John S. Unverzagt C. Angew. Chem. Int. Ed. 2014; 53: 12125
• 61b Murakami M. Kiuchi T. Nishihara M. Tezuka K. Okamoto R. Izumi M. Kajihara Y. Sci. Adv. 2016; 2: e1500678
• 61c Siman P. Karthikeyan SV. Nikolov M. Fischle W. Brik A. Angew. Chem. Int. Ed. 2013; 52: 8059
• 61d Bello C. Wang S. Meng L. Moremen KW. Becker CF. W. Angew. Chem. Int. Ed. 2015; 54: 7711
• 61e Tsuda Y. Shigenaga A. Tsuji K. Denda M. Sato K. Kitakaze K. Nakamura T. Inokuma T. Itoh K. Otaka A. ChemistryOpen 2015; 4: 448
• 61f Miyajima R. Tsuda Y. Inokuma T. Shigenaga A. Imanishi M. Futaki S. Otaka A. Pept. Sci. 2016; 106: 531
• 62 Thom J. Anderson D. McGregor J. Cotton G. Bioconjugate Chem. 2011; 22: 1017
• 63 Li Y.-M. Yang M.-Y. Huang Y.-C. Li Y.-T. Chen PR. Liu L. ACS Chem. Biol. 2012; 7: 1015
• 64 Adams AL. Macmillan D. J. Pept. Sci. 2013; 19: 65
• 65 Hondal RJ. Nilsson BL. Raines RT. J. Am. Chem. Soc. 2001; 123: 5140
• 66 Harris KM. Flemer S. Hondal RJ. J. Pept. Sci. 2007; 13: 81
• 67 Gieselman MD. Xie L. van der Donk WA. Org. Lett. 2001; 3: 1331
• 68 Roelfes G. Hilvert D. Angew. Chem. Int. Ed. 2003; 42: 2275
• 69 Muttenthaler M. Alewood PF. J. Pept. Sci. 2008; 14: 1223
• 70 Metanis N. Keinan E. Dawson PE. Angew. Chem. Int. Ed. 2010; 49: 7049
• 71 Ste Marie EJ. Ruggles EL. Hondal RJ. J. Pept. Sci. 2016; 22: 571
• 72 Raibaut L. Cargoet M. Ollivier N. Chang YM. Drobecq H. Boll E. Desmet R. Monbaliu J.-CM. Melnyk O. Chem. Sci. 2016; 7: 2657
• 73 Mitchell NJ. Malins LR. Liu X. Thompson RE. Chan B. Radom L. Payne RJ. J. Am. Chem. Soc. 2015; 137: 14011
• 74 Ollivier N. Blanpain A. Boll E. Raibaut L. Drobecq H. Melnyk O. Org. Lett. 2014; 16: 4032
• 75 Burlina F. Papageorgiou G. Morris C. White PD. Offer J. Chem. Sci. 2014; 5: 766
• 76 Cowper B. Sze TM. Premdjee B. Bongat White AF. Hacking A. Macmillan D. Chem. Commun. 2015; 51: 3208
• 77 Terrier VP. Adihou H. Arnould M. Delmas AF. Aucagne V. Chem. Sci. 2016; 7: 339
• 78a Hojo H. Onuma Y. Akimoto Y. Nakahara Y. Nakahara Y. Tetrahedron Lett. 2007; 48: 25
• 78b Hojo H. Org. Biomol. Chem. 2016; 14: 6368
• 78c Erlich LA. Kumar KS. A. Haj-Yahya M. Dawson PE. Brik A. Org. Biomol. Chem. 2010; 8: 2392
• 79 Zheng J.-S. Chen X. Tang S. Chang H.-N. Wang F.-L. Zuo C. Org. Lett. 2014; 16: 4908
• 80a Hemu X. Taichi M. Qiu Y. Liu D.-X. Tam JP. Pept. Sci. 2013; 100: 492
• 80b Taichi M. Hemu X. Qiu Y. Tam JP. Org. Lett. 2013; 15: 2620
• 81a Kang J. Macmillan D. Org. Biomol. Chem. 2010; 8: 1993
• 81b Macmillan D. Adams A. Premdjee B. Isr. J. Chem. 2011; 51: 885
• 81c Tailhades J. Patil NA. Hossain MA. Wade JD. J. Pept. Sci. 2015; 21: 139
• 82a Ollivier N. Dheur J. Mhidia R. Blanpain A. Melnyk O. Org. Lett. 2010; 12: 5238
• 82b Hou W. Zhang X. Li F. Liu C.-F. Org. Lett. 2011; 13: 386
• 82c Raibaut L. Adihou H. Desmet R. Delmas AF. Aucagne V. Melnyk O. Chem. Sci. 2013; 4: 4061
• 83a Tsuda S. Shigenaga A. Bando K. Otaka A. Org. Lett. 2009; 11: 823
• 83b Sato K. Shigenaga A. Tsuji K. Tsuda S. Sumikawa Y. Sakamoto K. Otaka A. ChemBioChem 2011; 12: 1840
• 83c Sato K. Shigenaga A. Kitakaze K. Sakamoto K. Tsuji D. Itoh K. Otaka A. Angew. Chem. Int. Ed. 2013; 52: 7855
• 84 Tsuda S. Mochizuki M. Sakamoto K. Denda M. Nishio H. Otaka A. Yoshiya T. Org. Lett. 2016; 18: 5940
• 85 Raibaut L. Ollivier N. Melnyk O. Chem. Soc. Rev. 2012; 41: 7001
• 86 Liu P. O’Mara BW. Warrack BM. Wu W. Huang Y. Zhang Y. Zhao R. Lin M. Ackerman MS. Hocknell PK. Chen G. Tao L. Rieble S. Wang J. Wang-Iverson DB. Tymiak AA. Grace MJ. Russell RJ. J. Am. Soc. Mass Spectrom. 2010; 21: 837
• 87 Rohde H. Schmalisch J. Harpaz Z. Diezmann F. Seitz O. ChemBioChem 2011; 12: 1396
• 88 Pavlov MY. Watts RE. Tan Z. Cornish VW. Ehrenberg M. Forster AC. Proc. Natl. Acad. Sci. USA 2009; 106: 50
• 89 Kawakami T. Ohta A. Ohuchi M. Ashigai H. Murakami H. Suga H. Nat. Chem. Biol. 2009; 5: 888
• 90 Hegemann JD. Zimmermann M. Xie X. Marahiel MA. Acc. Chem. Res. 2015; 48: 1909
• 91 Raibaut L. Drobecq H. Melnyk O. Org. Lett. 2015; 17: 3636
• 92 Nguyen DP. Elliott T. Holt M. Muir TW. Chin JW. J. Am. Chem. Soc. 2011; 133: 11418
• 93 Al Toma RS. Kuthning A. Exner MP. Denisiuk A. Ziegler J. Budisa N. Süssmuth RD. ChemBioChem 2015; 16: 503