Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 3597 2022-11-29 16:50:47 |
2 format correct Meta information modification 3597 2022-11-30 02:55:47 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Lee, Y.S. Peptidomimetics and Their Applications for Opioid Peptide Drug. Encyclopedia. Available online: https://encyclopedia.pub/entry/37163 (accessed on 21 April 2024).
Lee YS. Peptidomimetics and Their Applications for Opioid Peptide Drug. Encyclopedia. Available at: https://encyclopedia.pub/entry/37163. Accessed April 21, 2024.
Lee, Yeon Sun. "Peptidomimetics and Their Applications for Opioid Peptide Drug" Encyclopedia, https://encyclopedia.pub/entry/37163 (accessed April 21, 2024).
Lee, Y.S. (2022, November 29). Peptidomimetics and Their Applications for Opioid Peptide Drug. In Encyclopedia. https://encyclopedia.pub/entry/37163
Lee, Yeon Sun. "Peptidomimetics and Their Applications for Opioid Peptide Drug." Encyclopedia. Web. 29 November, 2022.
Peptidomimetics and Their Applications for Opioid Peptide Drug
Edit

Peptidomimetics are synthetically altered peptides with adjusted molecular properties for specific biological or therapeutic applications and have been an important class of drug molecules due to their potential features, high potency, and low toxicity since the term was created first in the late 1970s.

opioid receptors analgesic drugs bioavailability peptidomimetic

1. Opioid Receptors and Natural Opioid Peptides

Opioid receptors which belong to G-protein coupled receptors are known to be involved in pain modulation, numerous physiological functions, and behavioral effects and are characterized in three subtypes, mu- (MOR), delta- (DOR), and kappa-opioid receptor (KOR) with overall 60–65% high structural homology [1]. The extracellular region has much lower homology, and the differences in the region are responsible for the subtype-selectivity of endogenous opioid peptides [2]. There are three main families of the endogenous opioid peptides, END, ENK, and DYN, which are derived from three different precursor proteins, pro-ENK, pro-DYN, and pro-opiomelanocortin, and prefer to bind at the MOR, DOR, and KOR, respectively, with low selectivity but strong analgesic effects in vivo with milder side effects, unlike morphine [1]. Regardless of the receptor selectivity, all of the endogenous opioid peptides share the same N-terminal tetrapeptide sequence (YGGF) that acts as the message part for the receptor, while their C-terminal acts as the address part for selectivity (Table 1).
Table 1. Natural opioid peptides and their selectivities for the opioid receptors.

References

  1. Eguchi, M. Recent advances in selective opioid receptor agonists and antagonists. Med. Res. Rev. 2004, 24, 182–212.
  2. Onogi, T.; Minami, M.; Katao, Y.; Nakagawa, T.; Aoki, Y.; Toya, T.; Katsumata, S.; Satoh, M. DAMGO, a μ-opioid receptor selective agonist, distinguishes between μ-and δ-opioid receptors around their first extracellular loops. FEBS Lett. 1995, 357, 93–97.
  3. Handa, B.K.; Land, A.C.; Lord, J.A.; Morgan, B.A.; Rance, M.J.; Smith, C.F. Analogues of beta-LPH61-64 possessing selective agonist activity at mu-opiate receptors. Eur. J. Pharmacol. 1981, 70, 531–540.
  4. Koehl, A.; Hu, H.; Maeda, S.; Zhang, Y.; Qu, Q.; Paggi, J.M.; Latorraca, N.R.; Hilger, D.; Dawson, R.; Matile, H.; et al. Structure of the µ-opioid receptor–Gi protein complex. Nature 2018, 558, 547–552.
  5. Mosberg, H.I.; Hurst, R.; Hruby, V.J.; Gee, K.; Yamamura, H.I.; Galligan, J.J.; Burks, T.F. Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc. Natl. Acad. Sci. USA 1983, 80, 5871–5874.
  6. Wang, Y.; Kuczera, K. Molecular dynamics simulations of cyclic and linear DPDPE: Influence of the disulfide bond on peptide flexibility. J. Phys. Chem. 1996, 100, 2555–2563.
  7. Lung, F.D.; Meyer, J.P.; Lou, B.S.; Xiang, L.; Li, G.; Davis, P.; DeLeon, I.A.; Yamamura, H.I.; Porreca, F.; Hruby, V.J. Effects of modifications of residues in position 3 of dynorphin A(1-11)-NH2 on kappa receptor selectivity and potency. J. Med. Chem. 1996, 39, 2456–2460.
  8. Li, T.; Jinsmaa, Y.; Nedachi, M.; Miyazaki, A.; Tsuda, Y.; Ambo, A.; Sasaki, Y.; Bryant, S.D.; Marczak, E.; Li, Q.; et al. Transformation of mu-opioid receptor agonists into biologically potent mu-opioid receptor antagonists. Bioorg. Med. Chem. 2007, 15, 1237–1251.
  9. Fichna, J.; do-Rego, J.-C.; Kosson, P.; Costentin, J.; Janecka, A. Characterization of antinociceptive activity of novel endomorphin-2 and morphiceptin analogs modified in the third position. Biochem. Pharmacol. 2005, 69, 179–185.
  10. Schiller, P.W.; Berezowska, I.; Nguyen, T.M.-D.; Schmidt, R.; Lemieux, C.; Chung, N.N.; Falcone-Hindley, M.L.; Yao, W.; Liu, J.; Iwama, S. Novel ligands lacking a positive charge for the δ-and μ-opioid receptors. J. Med. Chem. 2000, 43, 551–559.
  11. Gairin, J.E.; Mazarguil, H.; Alvinerie, P.; Botanch, C.; Cros, J.; Meunier, J.C. N,N-diallyl-tyrosyl substitution confers antagonist properties on the kappa-selective opioid peptide dynorphin A(1-11). Br. J. Pharmacol. 1988, 95, 1023–1030.
  12. Schiller, P.W.; Weltrowska, G.; Nguyen, T.M.-D.; Lemieux, C.; Chung, N.N.; Lu, Y. Conversion of δ-, κ-and μ-Receptor Selective Opioid Peptide Agonists into δ-, κ-and μ-Selective Antagonists. Life Sci. 2003, 73, 691–698.
  13. Tancredi, T.; Salvadori, S.; Amodeo, P.; Picone, D.; Lazarus, L.H.; Bryant, S.D.; Guerrini, R.; Marzola, G.; Temussi, P.A. Conversion of enkephalin and dermorphin into delta-selective opioid antagonists by single-residue substitution. Eur. J. Biochem. 1994, 224, 241–247.
  14. Wang, L.; Wang, N.; Zhang, W.; Cheng, X.; Yan, Z.; Shao, G.; Wang, X.; Wang, R.; Fu, C. Therapeutic peptides: Current applications and future directions. Sign. Trans. Targeted Therap. 2022, 7, 1–27.
  15. Witt, K.A.; Davis, T.P. CNS drug delivery: Opioid peptides and the blood-brain barrier. AAPS J. 2006, 8, E76–E88.
  16. Lau, J.L.; Dunn, M.K. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg. Med. Chem. 2018, 26, 2700–2707.
  17. Gentilucci, L.; De Marco, R.; Cerisoli, L. Chemical modifications designed to improve peptide stability: Incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Curr. Pharm. Des. 2010, 16, 3185–3203.
  18. Pert, C.B.; Pert, A.; Chang, J.K.; Fong, B.T. (D-Ala2)-Met-enkephalinamide: A potent, long-lasting synthetic pentapeptide analgesic. Science 1976, 194, 330–332.
  19. Avan, I.; Hall, C.D.; Katritzky, A.R. Peptidomimetics via modifications of amino acids and peptide bonds. Chem. Soc. Rev. 2014, 43, 3575–3594.
  20. Roberts, L.R.; Brady, K.; Brown, A.; Davey, D.; Feng, L.; Huang, H.; Liu, D.; Malet, L.; McMurray, G.; Phelan, A.; et al. Kappa agonist CovX-Bodies. Bioorg. Med. Chem. Lett. 2012, 22, 4173–4178.
  21. Kropotova, E.S.; Ivleva, I.S.; Karpenko, M.N.; Mosevitsky, M.I. Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia. Bioorg. Med. Chem. 2020, 28, 115184.
  22. Beaudeau, J.L.; Blais, V.; Holleran, B.J.; Bergeron, A.; Pineyro, G.; Guerin, B.; Gendron, L.; Dory, Y.L. N-Guanidyl and C-Tetrazole Leu-Enkephalin Derivatives: Efficient Mu and Delta Opioid Receptor Agonists with Improved Pharmacological Properties. ACS Chem. Neurosci. 2019, 10, 1615–1626.
  23. Weber, S.J.; Abbruscato, T.J.; Brownson, E.A.; Lipkowski, A.W.; Polt, R.; Misicka, A.; Haaseth, R.C.; Bartosz, H.; Hruby, V.J.; Davis, T.P. Assessment of an in vitro blood-brain barrier model using several enkephalin opioid analogs. J. Pharmacol. Exp. Ther. 1993, 266, 1649–1655.
  24. Banks, W.A.; Kastin, A.J. Peptides and the blood-brain barrier: Lipophilicity as a predictor of permeability. Brain Res. Bullet. 1985, 15, 287–292.
  25. Hansen, D.W., Jr.; Stapelfeld, A.; Savage, M.A.; Reichman, M.; Hammond, D.L.; Haaseth, R.C.; Mosberg, H.I. Systemic analgesic activity and delta-opioid selectivity in enkephalin. J. Med. Chem. 1992, 35, 684–687.
  26. Weber, S.J.; Greene, D.L.; Sharma, S.D.; Yamamura, H.I.; Kramer, T.H.; Burks, T.F.; Hruby, V.J.; Hersh, L.B.; Davis, T.P. Distribution and analgesia of enkephalin and two halogenated analogs after intravenous administration. J. Pharmacol. Exp. Ther. 1991, 259, 1109–1117.
  27. Chandrakumar, N.S.; Stapelfeld, A.; Beardsley, P.M.; Lopez, O.T.; Drury, B.; Anthony, E.; Savage, M.A.; Williamson, L.N.; Reichman, M. Analogs of the. delta. opioid receptor selective cyclic peptide -enkephalin: 2’, 6’-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions. J. Med. Chem. 1992, 35, 2928–2938.
  28. Jinsmaa, Y.; Miyazaki, A.; Fujita, Y.; Li, T.; Fujisawa, Y.; Shiotani, K.; Tsuda, Y.; Yokoi, T.; Ambo, A.; Sasaki, Y.; et al. Oral bioavailability of a new class of micro-opioid receptor agonists containing 3,6-bis-2(1H)-pyrazinone with central-mediated analgesia. J. Med. Chem. 2004, 47, 2599–2610.
  29. Okada, Y.; Tsuda, Y.; Fujita, Y.; Yokoi, T.; Sasaki, Y.; Ambo, A.; Konishi, R.; Nagata, M.; Salvadori, S.; Jinsmaa, Y. Unique high-affinity synthetic μ-opioid receptor agonists with central-and systemic-mediated analgesia. J. Med. Chem. 2003, 46, 3201–3209.
  30. Wang, C.L.; Qiu, T.T.; Yang, D.J.; Yuan, B.Y.; Han, F.T.; Li, L.; Gu, N. Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects. Neuropharmacology 2017, 116, 98–109.
  31. Zhao, K.; Luo, G.; Zhao, G.M.; Schiller, P.W.; Szeto, H.H. Transcellular transport of a highly polar 3+ net charge opioid tetrapeptide. J. Pharmacol. Exp. Ther. 2003, 304, 425–432.
  32. Terasaki, T.; Hirai, K.; Sato, H.; Kang, Y.; Tsuji, A. Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078 into the blood-brain barrier. J. Pharmacol. Exp. Therap. 1989, 251, 351–357.
  33. Deguchi, Y.; Miyakawa, Y.; Sakurada, S.; Naito, Y.; Morimoto, K.; Ohtsuki, S.; Hosoya, K.I.; Terasaki, T. Blood–brain barrier transport of a novel µ1-specific opioid peptide, H-Tyr-d-Arg-Phe-β-Ala-OH (TAPA). J. Neurochem. 2003, 84, 1154–1161.
  34. Deguchi, Y.; Naito, Y.; Ohtsuki, S.; Miyakawa, Y.; Morimoto, K.; Hosoya, K.-I.; Sakurada, S.; Terasaki, T. Blood-brain barrier permeability of novel dermorphin (1–4) analogs: Transport property is related to the slow onset of antinociceptive activity in the central nervous system. J. Pharmacol. Exp. Therap. 2004, 310, 177–184.
  35. Polt, R.; Dhanasekaran, M.; Keyari, C.M. Glycosylated neuropeptides: A new vista for neuropsychopharmacology? Med. Res. Rev. 2005, 25, 557–585.
  36. Egleton, R.D.; Mitchell, S.A.; Huber, J.D.; Janders, J.; Stropova, D.; Polt, R.; Yamamura, H.I.; Hruby, V.J.; Davis, T.P. Improved bioavailability to the brain of glycosylated Met-enkephalin analogs. Brain Res. 2000, 881, 37–46.
  37. Egleton, R.D.; Mitchell, S.A.; Huber, J.D.; Palian, M.M.; Polt, R.; Davis, T.P. Improved blood-brain barrier penetration and enhanced analgesia of an opioid peptide by glycosylation. J. Pharmacol. Exp. Ther. 2001, 299, 967–972.
  38. Li, Y.; Lefever, M.R.; Muthu, D.; Bidlack, J.M.; Bilsky, E.J.; Polt, R. Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins. Fut. Med. Chem. 2012, 4, 205–226.
  39. Fichna, J.; Mazur, M.; Grzywacz, D.; Kamysz, W.; Perlikowska, R.; Piekielna, J.; Sobczak, M.; Salaga, M.; Toth, G.; Janecka, A.; et al. Novel glycosylated endomorphin-2 analog produces potent centrally-mediated antinociception in mice after peripheral administration. Bioorg. Med. Chem. Lett. 2013, 23, 6673–6676.
  40. Ballet, S.; Betti, C.; Novoa, A.; Tomboly, C.; Nielsen, C.U.; Helms, H.C.; Lesniak, A.; Kleczkowska, P.; Chung, N.N.; Lipkowski, A.W.; et al. In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt(1)-DALDA Analogues. ACS Med. Chem. Lett. 2014, 5, 352–357.
  41. Varamini, P.; Mansfeld, F.M.; Blanchfield, J.T.; Wyse, B.D.; Smith, M.T.; Toth, I. Synthesis and biological evaluation of an orally active glycosylated endomorphin-1. J. Med. Chem. 2012, 55, 5859–5867.
  42. Tomatis, R.; Marastoni, M.; Balboni, G.; Guerrini, R.; Capasso, A.; Sorrentino, L.; Santagada, V.; Caliendo, G.; Lazarus, L.H.; Salvadori, S. Synthesis and pharmacological activity of deltorphin and dermorphin-related glycopeptides. J. Med. Chem. 1997, 40, 2948–2952.
  43. Negri, L.; Lattanzi, R.; Tabacco, F.; Orru, L.; Severini, C.; Scolaro, B.; Rocchi, R. Dermorphin and deltorphin glycosylated analogues: Synthesis and antinociceptive activity after systemic administration. J. Med. Chem. 1999, 42, 400–404.
  44. Mosberg, H.I.; Yeomans, L.; Anand, J.P.; Porter, V.; Sobczyk-Kojiro, K.; Traynor, J.R.; Jutkiewicz, E.M. Development of a bioavailable mu opioid receptor (MOPr) agonist, delta opioid receptor (DOPr) antagonist peptide that evokes antinociception without development of acute tolerance. J. Med. Chem. 2014, 57, 3148–3153.
  45. Palian, M.M.; Boguslavsky, V.I.; O’Brien, D.F.; Polt, R. Glycopeptide-membrane interactions: Glycosyl enkephalin analogues adopt turn conformations by NMR and CD in amphipathic media. J. Am. Chem. Soc. 2003, 125, 5823–5831.
  46. Witt, K.A.; Huber, J.D.; Egleton, R.D.; Roberts, M.J.; Bentley, M.D.; Guo, L.; Wei, H.; Yamamura, H.I.; Davis, T.P. Pharmacodynamic and pharmacokinetic characterization of poly(ethylene glycol) conjugation to met-enkephalin analog -enkephalin (DPDPE). J. Pharmacol. Exp. Ther. 2001, 298, 848–856.
  47. Lindqvist, A.; Rip, J.; Gaillard, P.J.; Bjorkman, S.; Hammarlund-Udenaes, M. Enhanced brain delivery of the opioid peptide DAMGO in glutathione pegylated liposomes: A microdialysis study. Mol. Pharm. 2013, 10, 1533–1541.
  48. Greene, D.L.; Hau, V.S.; Abbruscato, T.J.; Bartosz, H.; Misicka, A.; Lipkowski, A.W.; Hom, S.; Gillespie, T.J.; Hruby, V.J.; Davis, T.P. Enkephalin analog prodrugs: Assessment of in vitro conversion, enzyme cleavage characterization and blood-brain barrier permeability. J. Pharmacol. Exp. Ther. 1996, 277, 1366–1375.
  49. Ouyang, H.; Tang, F.; Siahaan, T.J.; Borchardt, R.T. A modified coumarinic acid-based cyclic prodrug of an opioid peptide: Its enzymatic and chemical stability and cell permeation characteristics. Pharm. Res. 2002, 19, 794–801.
  50. Yang, J.Z.; Chen, W.; Borchardt, R.T. In vitro stability and in vivo pharmacokinetic studies of a model opioid peptide, H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE), and its cyclic prodrugs. J. Pharmacol. Exp. Ther. 2002, 303, 840–848.
  51. Prokai-Tatrai, K.; Kim, H.-S.; Prokai, L. The utility of oligopeptidase in brain-targeting delivery of an enkephalin analogue by prodrug design. Open Med. Chem. J. 2008, 2, 97.
  52. Liederer, B.M.; Borchardt, R.T. Stability of oxymethyl-modified coumarinic acid cyclic prodrugs of diastereomeric opioid peptides in biological media from various animal species including human. J. Pharm. Sci. 2005, 94, 2198–2206.
  53. Wang, J.; Hogenkamp, D.J.; Tran, M.; Li, W.-Y.; Yoshimura, R.F.; Johnstone, T.B.; Shen, W.-C.; Gee, K.W. Reversible lipidization for the oral delivery of leu-enkephalin. J. Drug Target. 2006, 14, 127–136.
  54. Ogawa, T.; Araki, M.; Miyamae, T.; Okayama, T.; Hagiwara, M.; Sakurada, S.; Morikawa, T. Synthesis and antinociceptive activity of orally active opioid peptides: Improvement of oral bioavailability by esterification. Chem. Pharm. Bull. 2003, 51, 759–771.
  55. Ogawa, T.; Miyamae, T.; Murayama, K.; Okuyama, K.; Okayama, T.; Hagiwara, M.; Sakurada, S.; Morikawa, T. Synthesis and structure-activity relationships of an orally available and long-acting analgesic peptide, N(alpha)-amidino-Tyr-D-Arg-Phe-MebetaAla-OH (ADAMB). J. Med. Chem. 2002, 45, 5081–5089.
  56. Machelska, H.; Celik, M.O. Advances in Achieving Opioid Analgesia Without Side Effects. Front. Pharmacol. 2018, 9, 1388.
  57. Anand, J.P.; Montgomery, D. Multifunctional Opioid Ligands. Handb. Exp. Pharmacol. 2018, 247, 21–51.
  58. Hruby, V.J. Multivalent peptide and peptidomimetic ligands for the treatment of pain without toxicities and addiction. Peptides 2019, 116, 63–67.
  59. Dietis, N.; Guerrini, R.; Calo, G.; Salvadori, S.; Rowbotham, D.J.; Lambert, D.G. Simultaneous targeting of multiple opioid receptors: A strategy to improve side-effect profile. Br. J. Anaesth 2009, 103, 38–49.
  60. Zhu, Y.; King, M.A.; Schuller, A.G.; Nitsche, J.F.; Reidl, M.; Elde, R.P.; Unterwald, E.; Pasternak, G.W.; Pintar, J.E. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice. Neuron 1999, 24, 243–252.
  61. Mosberg, H.I.; Yeomans, L.; Harland, A.A.; Bender, A.M.; Sobczyk-Kojiro, K.; Anand, J.P.; Clark, M.J.; Jutkiewicz, E.M.; Traynor, J.R. Opioid peptidomimetics: Leads for the design of bioavailable mixed efficacy mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist ligands. J. Med. Chem. 2013, 56, 2139–2149.
  62. Henry, S.; Anand, J.P.; Twarozynski, J.J.; Brinkel, A.C.; Pogozheva, I.D.; Sears, B.F.; Jutkiewicz, E.M.; Traynor, J.R.; Mosberg, H.I. Aromatic–Amine Pendants Produce Highly Potent and Efficacious Mixed Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Peptidomimetics with Enhanced Metabolic Stability. J. Med. Chem. 2020, 63, 1671–1683.
  63. Lee, Y.S.; Kulkarani, V.; Cowell, S.M.; Ma, S.W.; Davis, P.; Hanlon, K.E.; Vanderah, T.W.; Lai, J.; Porreca, F.; Vardanyan, R.; et al. Development of potent mu and delta opioid agonists with high lipophilicity. J. Med. Chem. 2011, 54, 382–386.
  64. Cowell, S.M.; Lee, Y.S. Biphalin: The Foundation of Bivalent Ligands. Curr. Med. Chem. 2016, 23, 3267–3284.
  65. Horan, P.J.; Mattia, A.; Bilsky, E.J.; Weber, S.; Davis, T.P.; Yamamura, H.I.; Malatynska, E.; Appleyard, S.M.; Slaninova, J.; Misicka, A.; et al. Antinociceptive profile of biphalin, a dimeric enkephalin analog. J. Pharmacol. Exp. Ther. 1993, 265, 1446–1454.
  66. Lowery, J.J.; Raymond, T.J.; Giuvelis, D.; Bidlack, J.M.; Polt, R.; Bilsky, E.J. In vivo characterization of MMP-2200, a mixed delta/mu opioid agonist, in mice. J. Pharmacol. Exp. Ther. 2011, 336, 767–778.
  67. Li, T.; Shiotani, K.; Miyazaki, A.; Tsuda, Y.; Ambo, A.; Sasaki, Y.; Jinsmaa, Y.; Marczak, E.; Bryant, S.D.; Lazarus, L.H.; et al. Bifunctional endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands. J. Med. Chem. 2007, 50, 2753–2766.
  68. Frederickson, R.C.; Smithwick, E.L.; Shuman, R.; Bemis, K.G. Metkephamid, a systemically active analog of methionine enkephalin with potent opioid alpha-receptor activity. Science 1981, 211, 603–605.
  69. Burkhardt, C.; Frederickson, R.C.; Pasternak, G.W. Metkephamid (Tyr-D-ala-Gly-Phe-N(Me)Met-NH2), a potent opioid peptide: Receptor binding and analgesic properties. Peptides 1982, 3, 869–871.
  70. Schiller, P.W.; Schmidt, R.; Weltrowska, G.; Berezowska, I.; Nguyen, T.M.-D.; Dupuis, S.; Chung, N.N.; Lemieux, C.; Wilkes, B.C.; Carpenter, K.A. Conformationally constrained opioid peptide analogs with novel activity profiles. Lett. Peptide Sci. 1998, 5, 209–214.
  71. Dietis, N.; McDonald, J.; Molinari, S.; Calo, G.; Guerrini, R.; Rowbotham, D.J.; Lambert, D.G. Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505). Br. J. Anaesth 2012, 108, 262–270.
  72. Purington, L.C.; Sobczyk-Kojiro, K.; Pogozheva, I.D.; Traynor, J.R.; Mosberg, H.I. Development and in vitro characterization of a novel bifunctional mu-agonist/delta-antagonist opioid tetrapeptide. ACS Chem. Biol. 2011, 6, 1375–1381.
  73. Harland, A.A.; Yeomans, L.; Griggs, N.W.; Anand, J.P.; Pogozheva, I.D.; Jutkiewicz, E.M.; Traynor, J.R.; Mosberg, H.I. Further optimization and evaluation of bioavailable, mixed-efficacy μ-opioid receptor (MOR) agonists/δ-opioid receptor (DOR) antagonists: Balancing MOR and DOR affinities. J. Med. Chem. 2015, 58, 8952–8969.
  74. Henry, S.P.; Fernandez, T.J.; Anand, J.P.; Griggs, N.W.; Traynor, J.R.; Mosberg, H.I. Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic mu-Opioid Receptor (MOR) Agonist/delta-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability. J. Med. Chem. 2019, 62, 4142–4157.
  75. Bender, A.M.; Clark, M.J.; Agius, M.P.; Traynor, J.R.; Mosberg, H.I. Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity mu opioid receptor (MOR) agonist/delta opioid receptor (DOR) antagonist ligands. Bioorg. Med. Chem. Lett. 2014, 24, 548–551.
  76. Lee, Y.S.; Remesic, M.; Ramos-Colon, C.; Wu, Z.; LaVigne, J.; Molnar, G.; Tymecka, D.; Misicka, A.; Streicher, J.M.; Hruby, V.J. Multifunctional Enkephalin Analogs with a New Biological Profile: MOR/DOR Agonism and KOR Antagonism. Biomedicines 2021, 9, 625.
  77. Perlikowska, R.; Malfacini, D.; Cerlesi, M.C.; Piekielna, J.; Floriot, L.; Henry, T.; Do-Rego, J.C.; Tömböly, C.; Kluczyk, A.; Janecka, A. Pharmacological characterization of endomorphin-2-based cyclic pentapeptides with methylated phenylalanine residues. Peptides 2014, 55, 145–150.
  78. Gach-Janczak, K.; Piekielna-Ciesielska, J.; Adamska-Bartłomiejczyk, A.; Perlikowska, R.; Kruszyński, R.; Kluczyk, A.; Krzywik, J.; Sukiennik, J.; Cerlesi, M.C.; Calo, G. Synthesis and activity of opioid peptidomimetics with β2-and β3-amino acids. Peptides 2017, 95, 116–123.
  79. Martinez, V.; Abalo, R. Peripherally acting opioid analgesics and peripherally-induced analgesia. Behav. Pharmacol. 2020, 31, 136–158.
  80. Zaitseva, N.; Galan, S.; Pavlova, L. Prospects of a search for kappa-opioid receptor agonists with analgesic activity. Pharm. Chem. J. 2018, 51, 843–851.
  81. Spampinato, S.; Qasem, A.R.; Calienni, M.; Murari, G.; Gentilucci, L.; Tolomelli, A.; Cardillo, G. Antinociception by a peripherally administered novel endomorphin-1 analogue containing beta-proline. Eur. J. Pharmacol. 2003, 469, 89–95.
  82. Hesselink, J.M.K. CR845 (Difelikefalin), A Kappa Receptors Agonist In Phase III By CARA Therapeutics: A Case Of ‘Spin’In Scientific Writing? J. Pharmacol. Clin. Res. 2017, 2, 555588.
  83. Wallace, M.S.; Moulin, D.; Clark, A.; Wasserman, R.; Neale, A.; Morley-Forster, P.; Castaigne, J.-P.; Teichman, S. A Phase II, multicenter, randomized, double-blind, placebo-controlled crossover study of CJC-1008—a long-acting, parenteral opioid analgesic—in the treatment of postherpetic neuralgia. J. Opioid. Manag. 2006, 2, 167–173.
  84. Tiwari, V.; Yang, F.; He, S.Q.; Shechter, R.; Zhang, C.; Shu, B.; Zhang, T.; Tiwari, V.; Wang, Y.; Dong, X.; et al. Activation of Peripheral mu-opioid Receptors by Dermorphin (1-4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain. Anesthesiology 2016, 124, 706–720.
  85. Posner, J.; Moody, S.; Peck, A.; Rutter, D.; Telekes, A. Analgesic, central, cardiovascular and endocrine effects of the enkephalin analogue Tyr-D. Arg-Gly-Phe (4NO 2)-Pro-NH 2 (443C81) in healthy volunteers. Eur. J. Clin. Pharmacol. 1990, 38, 213–218.
  86. Deeks, E.D. Difelikefalin: First Approval. Drugs 2021, 81, 1937–1944.
  87. DeWire, S.M.; Yamashita, D.S.; Rominger, D.H.; Liu, G.; Cowan, C.L.; Graczyk, T.M.; Chen, X.T.; Pitis, P.M.; Gotchev, D.; Yuan, C.; et al. A G protein-biased ligand at the mu-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J. Pharmacol. Exp. Ther. 2013, 344, 708–717.
  88. Piekielna-Ciesielska, J.; Wtorek, K.; Janecka, A. Biased Agonism as an Emerging Strategy in the Search for Better Opioid Analgesics. Curr. Med. Chem. 2020, 27, 1562–1575.
  89. He, L.; Gooding, S.W.; Lewis, E.; Felth, L.C.; Gaur, A.; Whistler, J.L. Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice. Neuropsychopharmacology 2021, 46, 2241–2249.
  90. Faouzi, A.; Varga, B.R.; Majumdar, S. Biased opioid ligands. Molecules 2020, 25, 4257.
  91. Madariaga-Mazón, A.; Marmolejo-Valencia, A.F.; Li, Y.; Toll, L.; Houghten, R.A.; Martinez-Mayorga, K. Mu-Opioid receptor biased ligands: A safer and painless discovery of analgesics? Drug Discov. Today 2017, 22, 1719–1729.
  92. Piekielna-Ciesielska, J.; Ferrari, F.; Calo, G.; Janecka, A. Cyclopeptide Dmt-NH2, a novel G protein-biased agonist of the mu opioid receptor. Peptides 2018, 101, 227–233.
  93. Bella Ndong, D.; Blais, V.; Holleran, B.J.; Proteau-Gagné, A.; Cantin-Savoie, I.; Robert, W.; Nadon, J.F.; Beauchemin, S.; Leduc, R.; Piñeyro, G. Exploration of the fifth position of leu-enkephalin and its role in binding and activating delta (DOP) and mu (MOP) opioid receptors. Peptide Sci. 2019, 111, e24070.
  94. Sharma, K.K.; Cassell, R.J.; Su, H.; Blaine, A.T. Modulating β Arrestin-2 Recruitment at the δ- and µ-Opioid Receptors; Cambridge Open Engage: Cambridge, UK, 2020.
  95. Cassell, R.J.; Sharma, K.K.; Su, H.; Cummins, B.R.; Cui, H.; Mores, K.L.; Blaine, A.T.; Altman, R.A.; van Rijn, R.M. The Meta-Position of Phe4 in Leu-enkephalin Regulates Potency, Selectivity, Functional Activity, and Signaling Bias at the Delta and Mu Opioid Receptors. Molecules 2019, 24, 4542.
  96. Kandasamy, R.; Hillhouse, T.M.; Livingston, K.E.; Kochan, K.E.; Meurice, C.; Eans, S.O.; Li, M.-H.; White, A.D.; Roques, B.P.; McLaughlin, J.P. Positive allosteric modulation of the mu-opioid receptor produces analgesia with reduced side effects. Proc. Natl. Acad. Sci. USA 2021, 118, e2000017118.
  97. Remesic, M.; Hruby, V.J.; Porreca, F.; Lee, Y.S. Recent Advances in the Realm of Allosteric Modulators for Opioid Receptors for Future Therapeutics. ACS Chem. Neurosci. 2017, 8, 1147–1158.
  98. Cowell, S.M.; Lee, Y.S.; Cain, J.P.; Hruby, V.J. Exploring Ramachandran and chi space: Conformationally constrained amino acids and peptides in the design of bioactive polypeptide ligands. Curr. Med. Chem. 2004, 11, 2785–2798.
  99. Yamazaki, T.; Ro, S.; Goodman, M.; Chung, N.N.; Schiller, P.W. A topochemical approach to explain morphiceptin bioactivity. J. Med. Chem. 1993, 36, 708–719.
  100. Granier, S.; Manglik, A.; Kruse, A.C.; Kobilka, T.S.; Thian, F.S.; Weis, W.I.; Kobilka, B.K. Structure of the delta-opioid receptor bound to naltrindole. Nature 2012, 485, 400–404.
  101. Chavkin, C.; Goldstein, A. Specific receptor for the opioid peptide dynorphin: Structure--activity relationships. Proc. Natl. Acad. Sci. USA 1981, 78, 6543–6547.
  102. Portoghese, P.S.; Sultana, M.; Takemori, A.E. Design of peptidomimetic delta opioid receptor antagonists using the message-address concept. J. Med. Chem. 1990, 33, 1714–1720.
  103. Schiller, P.W.; Nguyen, T.M.; Chung, N.N.; Lemieux, C. Dermorphin analogues carrying an increased positive net charge in their “message” domain display extremely high mu opioid receptor selectivity. J. Med. Chem. 1989, 32, 698–703.
  104. Borics, A.; Toth, G. Structural comparison of mu-opioid receptor selective peptides confirmed four parameters of bioactivity. J. Mol. Graph Model 2010, 28, 495–505.
  105. Lasota, A.; Frączak, O.; Muchowska, A.; Nowakowski, M.; Maciejczyk, M.; Ejchart, A.; Olma, A. Synthesis, Biological Activity, and NMR-Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a New α, α-Disubstituted Glycines. Chem. Biol. Drug Design 2016, 87, 824–832.
More
Information
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
View Times: 382
Revisions: 2 times (View History)
Update Date: 30 Nov 2022
1000/1000