Conjugation Approaches for Peptide-Mediated Delivery of Oligonucleotides Therapeutics

Nitin A. Patil

doi:10.1071/CH21131

REVIEW (Open Access)

Previous Next Contents Vol 75(2)

Conjugation Approaches for Peptide-Mediated Delivery of Oligonucleotides Therapeutics

Nitin A. Patil

^A

+ Author Affiliations

- Author Affiliations

^A Biomedicine Discovery Institute, Monash University, Clayton, Vic. 3800, Australia. Email: nitin.patil@monash.edu

Dr Nitin Patil is an Australian National Health and Medical Research Council's Peter Doherty Fellow at Monash University. He leads the chemistry team in the laboratory of Antimicrobial System Pharmacology. The overarching aim of his research is to address challenges of drug-resistant pathogenic bacteria by developing peptide and oligonucleotide-based therapeutics.

Australian Journal of Chemistry 75(2) 24-33 https://doi.org/10.1071/CH21131
Submitted: 31 May 2021 Accepted: 12 August 2021 Published: 7 September 2021

Journal Compilation © CSIRO 2022 Open Access CC BY

Abstract

Oligonucleotide-based agents are versatile biomolecules that modulate gene expression. The last decade has seen the emergence of oligonucleotide-based tools for biochemical investigations. Importantly, several oligonucleotide-based drugs and vaccines are currently used for various therapeutic applications ranging from anti-inflammatory and anti-viral agents to those used in cardiovascular, ophthalmic, and neuro-muscular disorders. Despite a broad range of applications, achieving efficient oligonucleotide delivery remains a major limitation. A possible solution is to conjugate cell-penetrating peptides with oligonucleotides. This review provides an overview of chemical strategies used to synthesise peptide–oligonucleotide conjugates. The merits and liabilities of these strategies are discussed in the context of synthetic efficiency, and bio-reversible and -irreversible linkages.

Keywords: conjugation, oligonucleotide, peptide, peptide nucleic acids, drug delivery, thiol–maleimide conjugation, click chemistry, 2-cyanoisoicotinamide (CINA) linkage.

References

[1] C. F. Bennett, E. E. Swayze, Annu. Rev. Pharmacol. Toxicol. 2010, 50, 259.
| Crossref | GoogleScholarGoogle Scholar | 20055705PubMed |

[2] D. P. Potaczek, H. Garn, S. D. Unger, H. Renz, J. Allergy Clin. Immunol. 2016, 137, 1334.
| Crossref | GoogleScholarGoogle Scholar | 27155029PubMed |

[3] T. C. Roberts, R. Langer, M. J. A. Wood, Nat. Rev. Drug Discov. 2020, 19, 673.
| Crossref | GoogleScholarGoogle Scholar | 32782413PubMed |

[4] R. Gambari, Expert Opin. Ther. Pat. 2014, 24, 267.
| Crossref | GoogleScholarGoogle Scholar | 24405414PubMed |

[5] A. A. Koshkin, P. Nielsen, M. Meldgaard, V. K. Rajwanshi, S. K. Singh, J. Wengel, J. Am. Chem. Soc. 1998, 120, 13252.
| Crossref | GoogleScholarGoogle Scholar |

[6] R. S. Finkel, C. A. Chiriboga, J. Vajsar, J. W. Day, J. Montes, D. C. De Vivo, M. Yamashita, F. Rigo, G. Hung, E. Schneider, D. A. Norris, S. Xia, C. F. Bennett, K. M. Bishop, Lancet 2016, 388, 3017.
| Crossref | GoogleScholarGoogle Scholar | 27939059PubMed |

[7] J. J. Dowling, Nat. Rev. Neurol. 2016, 12, 675.
| Crossref | GoogleScholarGoogle Scholar | 27857122PubMed |

[8] J. Summerton, D. Weller, Antisense Nucleic Acid Drug Dev. 1997, 7, 187.
| Crossref | GoogleScholarGoogle Scholar | 9212909PubMed |

[9] A. Porcheddu, G. Giacomelli, Curr. Med. Chem. 2005, 12, 2561.
| Crossref | GoogleScholarGoogle Scholar | 16248816PubMed |

[10] C. Sharma, S. K. Awasthi, Chem. Biol. Drug Des. 2017, 89, 16.
| 27490868PubMed |

[11] T. H. S. Tan, D. T. Hickman, J. Morral, I. G. Beadham, J. Micklefield, Chem. Commun. 2004, 516.
| Crossref | GoogleScholarGoogle Scholar |

[12] L. Huang, Y. Liu, Annu. Rev. Biomed. Eng. 2011, 13, 507.
| Crossref | GoogleScholarGoogle Scholar | 21639780PubMed |

[13] H. Yin, R. L. Kanasty, A. A. Eltoukhy, A. J. Vegas, J. R. Dorkin, D. G. Anderson, Nat. Rev. Genet. 2014, 15, 541.
| Crossref | GoogleScholarGoogle Scholar | 25022906PubMed |

[14] K. Lu, Q.-P. Duan, L. Ma, D.-X. Zhao, Bioconjug. Chem. 2010, 21, 187.
| Crossref | GoogleScholarGoogle Scholar | 19856957PubMed |

[15] M. E. Davis, J. E. Zuckerman, C. H. J. Choi, D. Seligson, A. Tolcher, C. A. Alabi, Y. Yen, J. D. Heidel, A. Ribas, Nature 2010, 464, 1067.
| Crossref | GoogleScholarGoogle Scholar | 20305636PubMed |

[16] O. M. Merkel, T. Kissel, J. Control. Release 2014, 190, 415.
| Crossref | GoogleScholarGoogle Scholar | 24933599PubMed |

[17] D. W. Pack, A. S. Hoffman, S. Pun, P. S. Stayton, Nat. Rev. Drug Discov. 2005, 4, 581.
| Crossref | GoogleScholarGoogle Scholar | 16052241PubMed |

[18] T. Lehto, E. Wagner, Nanomedicine 2014, 9, 2843.
| Crossref | GoogleScholarGoogle Scholar | 25535686PubMed |

[19] K. Phelps, A. Morris, P. A. Beal, ACS Chem. Biol. 2012, 7, 100.
| Crossref | GoogleScholarGoogle Scholar | 22148740PubMed |

[20] R. L. Juliano, X. Ming, O. Nakagawa, Acc. Chem. Res. 2012, 45, 1067.
| Crossref | GoogleScholarGoogle Scholar | 22353142PubMed |

[21] J. Winkler, Ther. Deliv. 2013, 4, 791.
| Crossref | GoogleScholarGoogle Scholar | 23883124PubMed |

[22] T. Coursindel, P. Järver, M. J. Gait, Nucleic Acid Ther. 2012, 22, 71.
| Crossref | GoogleScholarGoogle Scholar | 22409235PubMed |

[23] H. M. Moulton, J. D. Moulton, Biomembranes 2010, 1798, 2296.
| Crossref | GoogleScholarGoogle Scholar |

[24] U. Lächelt, E. Wagner, Chem. Rev. 2015, 115, 11043.
| Crossref | GoogleScholarGoogle Scholar | 25872804PubMed |

[25] R. L. Juliano, Nucleic Acids Res. 2016, 44, 6518.
| Crossref | GoogleScholarGoogle Scholar | 27084936PubMed |

[26] R. Juliano, M. R. Alam, V. Dixit, H. Kang, Nucleic Acids Res. 2008, 36, 4158.
| Crossref | GoogleScholarGoogle Scholar | 18558618PubMed |

[27] S. Benizri, A. Gissot, A. Martin, B. Vialet, M. W. Grinstaff, P. Barthélémy, Bioconjug. Chem. 2019, 30, 366.
| Crossref | GoogleScholarGoogle Scholar | 30608140PubMed |

[28] T. Lehto, K. Ezzat, M. J. A. Wood, S. El Andaloussi, Adv. Drug Deliv. Rev. 2016, 106, 172.
| Crossref | GoogleScholarGoogle Scholar | 27349594PubMed |

[29] F. Muttach, A. Rentmeister, Methods 2016, 107, 3.
| Crossref | GoogleScholarGoogle Scholar | 26884260PubMed |

[30] P. L. Patel, N. K. Rana, M. R. Patel, S. D. Kozuch, D. Sabatino, ChemMedChem 2016, 11, 252.
| Crossref | GoogleScholarGoogle Scholar | 26663095PubMed |

[31] J. Haralambidis, M. Chai, G. W. Tregear, Nucleic Acids Res. 1987, 15, 4857.
| Crossref | GoogleScholarGoogle Scholar | 3110740PubMed |

[32] P. Nielsen, M. Egholm, R. Berg, O. Buchardt, Science 1991, 254, 1497.
| Crossref | GoogleScholarGoogle Scholar | 1962210PubMed |

[33] P. Sazani, F. Gemignani, S.-H. Kang, M. A. Maier, M. Manoharan, M. Persmark, D. Bortner, R. Kole, Nat. Biotechnol. 2002, 20, 1228.
| Crossref | GoogleScholarGoogle Scholar | 12426578PubMed |

[34] J. Tailhades, H. Takizawa, M. J. Gait, D. A. Wellings, J. D. Wade, Y. Aoki, F. Shabanpoor, Front Chem. 2017, 5, 81.
| Crossref | GoogleScholarGoogle Scholar | 29094037PubMed |

[35] T. Soudah, S. Khawaled, R. I. Aqeilan, E. Yavin, ACS Omega 2019, 4, 13954.
| Crossref | GoogleScholarGoogle Scholar | 31497713PubMed |

[36] J. Winkler, E. Urban, D. Losert, V. Wacheck, H. Pehamberger, C. R. Noe, Nucleic Acids Res. 2004, 32, 710.
| Crossref | GoogleScholarGoogle Scholar | 14757835PubMed |

[37] J. Winkler, E. Urban, C. R. Noe, Bioconjug. Chem. 2005, 16, 1038.
| Crossref | GoogleScholarGoogle Scholar | 16029048PubMed |

[38] J. Winkler, M. Gilbert, A. Kocourková, M. Stessl, C. R. Noe, ChemMedChem 2008, 3, 102.
| Crossref | GoogleScholarGoogle Scholar | 17979170PubMed |

[39] K. Shinbara, W. Liu, R. H. P. van Neer, T. Katoh, H. Suga, Front Chem. 2020, 8, 447.
| Crossref | GoogleScholarGoogle Scholar | 32626683PubMed |

[40] M. Kye, Z. Zhang, Y.-b. Lim, Pept. Sci. 2021, 113, e24193.
| Crossref | GoogleScholarGoogle Scholar |

[41] P. Dawson, T. Muir, I. Clark-Lewis, S. Kent, Science 1994, 266, 776.
| Crossref | GoogleScholarGoogle Scholar | 7973629PubMed |

[42] R. K. Bruick, P. E. Dawson, S. B. H. Kent, N. Usman, G. F. Joyce, Chem. Biol. 1996, 3, 49.
| Crossref | GoogleScholarGoogle Scholar | 8807828PubMed |

[43] O. Zavoiura, U. Resch-Genger, O. Seitz, Bioconjug. Chem. 2018, 29, 1690.
| Crossref | GoogleScholarGoogle Scholar | 29694033PubMed |

[44] M. Lovrinovic, R. Seidel, R. Wacker, H. Schroeder, O. Seitz, M. Engelhard, R. S. Goody, C. M. Niemeyer, Chem. Commun. 2003, 822.
| Crossref | GoogleScholarGoogle Scholar |

[45] S. Ficht, A. Mattes, O. Seitz, J. Am. Chem. Soc. 2004, 126, 9970.
| Crossref | GoogleScholarGoogle Scholar | 15303871PubMed |

[46] M. McPherson, M. C. Wright, P. A. Lohse, Synlett 1999, 978.
| Crossref | GoogleScholarGoogle Scholar |

[47] J. Sayers, R. J. Payne, N. Winssinger, Chem. Sci. 2018, 9, 896.
| Crossref | GoogleScholarGoogle Scholar | 29629156PubMed |

[48] D. A. Stetsenko, M. J. Gait, J. Org. Chem. 2000, 65, 4900.
| Crossref | GoogleScholarGoogle Scholar | 10956469PubMed |

[49] M. Dastpeyman, J. A. Karas, A. Amin, B. J. Turner, F. Shabanpoor, Front Chem. 2021, 9, 627329.
| Crossref | GoogleScholarGoogle Scholar | 33738276PubMed |

[50] J. Tailhades, N. A. Patil, M. A. Hossain, J. D. Wade, J. Pept. Sci. 2015, 21, 139.
| Crossref | GoogleScholarGoogle Scholar | 25641053PubMed |

[51] S. Ficht, C. Dose, O. Seitz, ChemBioChem 2005, 6, 2098.
| Crossref | GoogleScholarGoogle Scholar | 16208732PubMed |

[52] G. Saito, J. A. Swanson, K.-D. Lee, Adv. Drug Deliv. Rev. 2003, 55, 199.
| Crossref | GoogleScholarGoogle Scholar | 12564977PubMed |

[53] J. Y. Legendre, A. Trzeciak, B. Bohrmann, U. Deuschle, E. Kitas, A. Supersaxo, Bioconjug. Chem. 1997, 8, 57.
| Crossref | GoogleScholarGoogle Scholar | 9026036PubMed |

[54] E. Wagner, C. Plank, K. Zatloukal, M. Cotten, M. L. Birnstiel, Proc. Natl. Acad. Sci. USA 1992, 89, 7934.
| Crossref | GoogleScholarGoogle Scholar | 1518816PubMed |

[55] D. R. Corey, D. Munoz-Medellin, A. Huang, Bioconjug. Chem. 1995, 6, 93.
| Crossref | GoogleScholarGoogle Scholar | 7711111PubMed |

[56] F. M. Uckun, S. Qazi, I. Dibirdik, D. E. Myers, Integr. Biol. 2013, 5, 122.
| Crossref | GoogleScholarGoogle Scholar |

[57] R. Eritja, A. Pons, M. Escarcellar, E. Giralt, F. Albericio, Tetrahedron 1991, 47, 4113.
| Crossref | GoogleScholarGoogle Scholar |

[58] J.-P. Bongartz, A.-M. Aubertain, P. G. Milhaud, B. Lebleu, Nucleic Acids Res. 1994, 22, 4681.
| Crossref | GoogleScholarGoogle Scholar | 7984418PubMed |

[59] J. J. Turner, D. Williams, D. Owen, M. J. Gait, Curr. Protoc. Nucleic Acid Chem. 2006, 24, 4.28.1.
| Crossref | GoogleScholarGoogle Scholar |

[60] N. A. Patil, J. A. Karas, J. D. Wade, M. A. Hossain, J. Tailhades, Chem. – Eur. J. 2019, 25, 8599.
| Crossref | GoogleScholarGoogle Scholar | 30924212PubMed |

[61] K. Arar, A.-M. Aubertin, A.-C. Roche, M. Monsigny, R. Mayer, Bioconjug. Chem. 1995, 6, 573.
| Crossref | GoogleScholarGoogle Scholar | 8974456PubMed |

[62] S. Abes, G. D. Ivanova, R. Abes, A. A. Arzumanov, D. Williams, D. Owen, B. Lebleu, M. J. Gait, in Macromolecular Drug Delivery: Methods and Protocols (Ed. M. Belting) 2009, pp. 85–99 (Humana Press: Totowa, NJ).

[63] H. Yin, A. F. Saleh, C. Betts, P. Camelliti, Y. Seow, S. Ashraf, A. Arzumanov, S. Hammond, T. Merritt, M. J. Gait, M. J. A. Wood, Mol. Ther. 2011, 19, 1295.
| Crossref | GoogleScholarGoogle Scholar | 21505427PubMed |

[64] N. A. Patil, J. A. Karas, B. J. Turner, F. Shabanpoor, Bioconjug. Chem. 2019, 30, 793.
| Crossref | GoogleScholarGoogle Scholar | 30645945PubMed |

[65] X. Ming, M. R. Alam, M. Fisher, Y. Yan, X. Chen, R. L. Juliano, Nucleic Acids Res. 2010, 38, 6567.
| Crossref | GoogleScholarGoogle Scholar | 20551131PubMed |

[66] M. Dastpeyman, R. Sharifi, A. Amin, J. A. Karas, B. Cuic, Y. Pan, J. A. Nicolazzo, B. J. Turner, F. Shabanpoor, Int. J. Pharm. 2021, 599, 120398.
| Crossref | GoogleScholarGoogle Scholar | 33640427PubMed |

[67] N. J. Ede, G. W. Tregear, J. Haralambidis, Bioconjug. Chem. 1994, 5, 373.
| Crossref | GoogleScholarGoogle Scholar | 7948105PubMed |

[68] M. R. Alam, X. Ming, M. Fisher, J. G. Lackey, K. G. Rajeev, M. Manoharan, R. L. Juliano, Bioconjug. Chem. 2011, 22, 1673.
| Crossref | GoogleScholarGoogle Scholar | 21755983PubMed |

[69] A. D. Baldwin, K. L. Kiick, Bioconjug. Chem. 2011, 22, 1946.
| Crossref | GoogleScholarGoogle Scholar | 21863904PubMed |

[70] Y. Kim, S. O. Ho, N. R. Gassman, Y. Korlann, E. V. Landorf, F. R. Collart, S. Weiss, Bioconjug. Chem. 2008, 19, 786.
| Crossref | GoogleScholarGoogle Scholar | 18275130PubMed |

[71] L. P. T. Hong, J. A. Scoble, L. Doughty, G. Coia, C. C. Williams, Aust. J. Chem. 2011, 64, 779.
| Crossref | GoogleScholarGoogle Scholar |

[72] H. Wu, P. J. LeValley, T. Luo, A. M. Kloxin, K. L. Kiick, Bioconjug. Chem. 2018, 29, 3595.
| Crossref | GoogleScholarGoogle Scholar | 30285419PubMed |

[73] S. D. Fontaine, R. Reid, L. Robinson, G. W. Ashley, D. V. Santi, Bioconjug. Chem. 2015, 26, 145.
| Crossref | GoogleScholarGoogle Scholar | 25494821PubMed |

[74] M. Jbara, J. Rodriguez, H. H. Dhanjee, A. Loas, S. L. Buchwald, B. L. Pentelute, Angew. Chem. Int. Ed. Engl. 2021, 60, 12109.
| Crossref | GoogleScholarGoogle Scholar | 33730425PubMed |

[75] B. Seelig, A. Jäschke, Tetrahedron Lett. 1997, 38, 7729.
| Crossref | GoogleScholarGoogle Scholar |

[76] K. W. Hill, J. Taunton-Rigby, J. D. Carter, E. Kropp, K. Vagle, W. Pieken, D. P. C. McGee, G. M. Husar, M. Leuck, D. J. Anziano, D. P. Sebesta, J. Org. Chem. 2001, 66, 5352.
| Crossref | GoogleScholarGoogle Scholar | 11485455PubMed |

[77] V. Borsenberger, S. Howorka, Nucleic Acids Res. 2009, 37, 1477.
| Crossref | GoogleScholarGoogle Scholar | 19139071PubMed |

[78] V. Marchán, S. Ortega, D. Pulido, E. Pedroso, A. Grandas, Nucleic Acids Res. 2006, 34, e24.
| Crossref | GoogleScholarGoogle Scholar | 16478710PubMed |

[79] D. Forget, D. Boturyn, E. Defrancq, J. Lhomme, P. Dumy, Chem. – Eur. J. 2001, 7, 3976.
| Crossref | GoogleScholarGoogle Scholar | 11596939PubMed |

[80] Y. Singh, O. P. Edupuganti, M. Villien, É. Defrancq, P. Dumy, C. R. Chim. 2005, 8, 789.
| Crossref | GoogleScholarGoogle Scholar |

[81] O. P. Edupuganti, O. Renaudet, E. Defrancq, P. Dumy, Bioorg. Med. Chem. Lett. 2004, 14, 2839.
| Crossref | GoogleScholarGoogle Scholar | 15125943PubMed |

[82] S. Ghosh, E. Defrancq, J. H. Lhomme, P. Dumy, S. Bhattacharya, Bioconjug. Chem. 2004, 15, 520.
| Crossref | GoogleScholarGoogle Scholar | 15149179PubMed |

[83] T. Hamma, P. S. Miller, Bioconjug. Chem. 2003, 14, 320.
| Crossref | GoogleScholarGoogle Scholar | 12643742PubMed |

[84] N. Ollivier, C. Olivier, C. Gouyette, T. Huynh-Dinh, H. Gras-Masse, O. Melnyk, Tetrahedron Lett. 2002, 43, 997.
| Crossref | GoogleScholarGoogle Scholar |

[85] Y. Anno, T. Kubo, R. Ueki, M. Yano, K. Sasaki, H. Ohba, M. Fujii, Nucleosides Nucleotides Nucleic Acids 2003, 22, 1451.
| Crossref | GoogleScholarGoogle Scholar | 14565440PubMed |

[86] T. Kubo, M. Morikawa, H. Ohba, M. Fujii, Org. Lett. 2003, 5, 2623.
| Crossref | GoogleScholarGoogle Scholar | 12868874PubMed |

[87] T. Kubo, Z. Zhelev, B. Rumiana, H. Ohba, K. Doi, M. Fujii, Org. Biomol. Chem. 2005, 3, 3257.
| Crossref | GoogleScholarGoogle Scholar | 16132084PubMed |

[88] B. B. Kasten, X. Ma, H. Liu, T. R. Hayes, C. L. Barnes, S. Qi, K. Cheng, S. C. Bottorff, W. S. Slocumb, J. Wang, Z. Cheng, P. D. Benny, Bioconjug. Chem. 2014, 25, 579.
| Crossref | GoogleScholarGoogle Scholar | 24568284PubMed |

[89] C. S. McKay, M. G. Finn, Chem. Biol. 2014, 21, 1075.
| Crossref | GoogleScholarGoogle Scholar | 25237856PubMed |

[90] A. H. El-Sagheer, T. Brown, Chem. Soc. Rev. 2010, 39, 1388.
| Crossref | GoogleScholarGoogle Scholar | 20309492PubMed |

[91] J. Willibald, J. Harder, K. Sparrer, K.-K. Conzelmann, T. Carell, J. Am. Chem. Soc. 2012, 134, 12330.
| Crossref | GoogleScholarGoogle Scholar | 22812910PubMed |

[92] D. C. Dieterich, J. J. L. Hodas, G. Gouzer, I. Y. Shadrin, J. T. Ngo, A. Triller, D. A. Tirrell, E. M. Schuman, Nat. Neurosci. 2010, 13, 897.
| Crossref | GoogleScholarGoogle Scholar | 20543841PubMed |

[93] T. S. Zatsepin, D. A. Stetsenko, A. A. Arzumanov, E. A. Romanova, M. J. Gait, T. S. Oretskaya, Bioconjug. Chem. 2002, 13, 822.
| Crossref | GoogleScholarGoogle Scholar | 12121138PubMed |

[94] K. Braun, P. Peschke, R. Pipkorn, S. Lampel, M. Wachsmuth, W. Waldeck, E. Friedrich, J. Debus, J. Mol. Biol. 2002, 318, 237.
| Crossref | GoogleScholarGoogle Scholar | 12051833PubMed |

[95] N. A. Patil, J.-P. Quek, B. Schroeder, R. Morewood, J. Rademann, D. Luo, C. Nitsche, ACS Med. Chem. Lett. 2021, 12, 732.
| Crossref | GoogleScholarGoogle Scholar | 34055219PubMed |