Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins

Future Medicinal Chemistry

Volumn 4, Issue 2, 2012, Pages 205-226

  Li, Yingxue ^a   Lefever, Mark R ^a   Muthu, Dhanasekaran ^a   Bidlack, Jean M ^b   Bilsky, Edward J ^c   Polt, Robin ^a  

^a University of Arizona   (United States)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

^c UNIVERSITY OF NEW ENGLAND   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [ALPHA (4 ALLYL 2,5 DIMETHYL 1 PIPERAZINYL) 3 HYDROXYBENZYL] N,N DIETHYLBENZAMIDE; ALPHA ENDORPHIN; AMINOSUGAR; BENZOPHENONE DERIVATIVE; BETA ENDORPHIN; BROMINE DERIVATIVE; DELTA OPIATE RECEPTOR; DEOXYSUGAR; DISULFIDE; DODECYL SULFATE SODIUM; GABAPENTIN; GAMMA ENDORPHIN; GLUCOSIDE; GLYCOPEPTIDE; INDIUM 111; KAPPA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR AGONIST; LEUCINE ENKEPHALIN; LIGAND; MANNOSE; METENKEPHALIN; MORPHINE; MU OPIATE RECEPTOR; N (2,7 DIMETHYL 9 FLUORENYLMETHOXYCARBONYL)LEUCINE; OPIATE; PENICILLAMINE; PLASMA PROTEIN; THREONINE; UNINDEXED DRUG; XYLOSE;

ADDICTION; BIOAVAILABILITY; BLOOD BRAIN BARRIER; CARBOXY TERMINAL SEQUENCE; CARDIOVASCULAR SYSTEM; CELL ASSAY; CELL COMPARTMENTALIZATION; CENTRAL NERVOUS SYSTEM; CHO CELL; CHRONIC PAIN; DEPRESSION; DRUG DISTRIBUTION; DRUG INDUSTRY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; ENDOTHELIUM CELL; GASTROINTESTINAL TRACT; GLYCOPROTEIN SYNTHESIS; GLYCOSYLATION; HUMAN; IMMUNE SYSTEM; INFLAMMATION; LIPOPHILICITY; MICROWAVE COOKING; MOLECULAR WEIGHT; NEUROPATHIC PAIN; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL; PROTEIN BINDING; RECEPTOR BINDING; REVIEW; TISSUE INJURY;

AMINO ACID SEQUENCE; ANALGESICS, OPIOID; BLOOD-BRAIN BARRIER; ENDORPHINS; ENKEPHALINS; GLYCOPEPTIDES; GLYCOSYLATION; HUMANS; MOLECULAR SEQUENCE DATA;

EID: 84863063484     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.11.195     Document Type: Review

References (107)

1. Borsook D, Hargreaves RJ, Becerra L. Can functional magnetic resonance imaging improve success rates in central nervous system drug discovery? Expert Opin. Drug Disc. 6, 597-617 (2011).
2. Banks WA. Delivery of peptides to the brain: emphasis on therapeutic development. Biopolymers 90, 589-594 (2008).
3. Begley DJ. Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol. Therap. 104, 29-45 (2004). (Pubitemid 39410561)
4. Pardridge WM. Brain Drug Targeting. Cambridge University Press, Cambridge, UK (2001).
5. Gruber CW, Muttenthaler M, Freissmuth M. Ligand-based peptide design and combinatorial peptide libraries to target G protein-coupled receptors. Curr. Pharm. Des. 16(28), 3071-3088 (2010).
6. Ibáñez CF. Beyond the cell surface: new mechanisms of receptor function. Biochem. Biophys. Res. Commun. 396(1), 24-27 (2010).
7. Cleland JL, Langer R. Formulation and Delivery of Proteins and Peptides. American Chemical Society, Washington, DC, USA (1994).
8. Taylor MD, Amidon GL. Peptide-Based Drug Design. American Chemical Society, Washington, DC, USA (1995).
9. Van der Walle C. Peptide and Protein Delivery. Academic Press, London, UK (2011).
10. Snyder SH. Opiate receptors and beyond: 30 years of neural signaling research. Neuropharmacology 47, 274-285 (2004). (Pubitemid 39298270)
11. Lagerström MC, Schiöth HB. Structural diversity of G protein coupled receptors and significance for drug discovery. Nature Rev. Drug Disc. 7, 339-357 (2008).
12. Tyndall JDA, Pfeiffer B, Abbenante G, Fairlie DP. Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure. Chem. Rev. 105, 793-826 (2005). (Pubitemid 40527376)
13. Martin WR, Eades CG, Thompson JA et al. The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther. 197, 517-532 (1976).
14. Evans CJ. Secrets of the opium poppy revealed. Neuropharmacology 47, 293-299 (2004). (Pubitemid 39298272)
15. Chang K-J, Porreca F, Woods J. The Delta Receptor. Marcel Dekker, Inc., NY, USA (2004).
16. Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW. Endogenous opioid peptides: multiple agonists and receptors. Nature 267, 495-499 (1977). (Pubitemid 8098466)
17. Yue X, Falk T, Zuniga LA et al. Effects of the novel glycopeptide opioid agonist MMP- 2200 in preclinical models of Parkinson's disease. Brain Res. 1413, 72-83 (2011).
18. Neumeyer JL, Zhang A, Xiong W et al. Design and synthesis of novel dimeric morphinan ligands for kappa and micro opioid receptors. J. Med. Chem. 46, 5162-5170 (2003). (Pubitemid 37414186)
19. Jordan BA, Devi L. G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399, 697-700 (1999). (Pubitemid 29289066)
20. Bhushan RG, Sharma SK, Xie Z et al. A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers. J. Med. Chem. 47, 2969-2972 (2004). (Pubitemid 38702692)
21. Simantov R, Kuhar MJ, Uhl GR et al. Opioid peptide enkephalin: Immunohistochemical mapping in rat central nervous system. Proc. Natl Acad. Sci. USA 74, 2167-2171 (1977). (Pubitemid 8103651)
22. Scherrer G, Imamachi N, Cao Y-Q et al. Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell 137, 1148-1159 (2009).
23. Schiller PW. Bi- or multifunctional opioid peptide drugs. Life Sci. 86, 598-603 (2010).
24. Pradhan AA, Befort K, Nozaki C et al. The delta opioid receptor: an evolving target for the treatment of brain disorders. TIPS 32, 581-590 (2011).
25. Patkar KA, Murray TF, Aldrich JV. The effects of C-terminal modifications on the opioid activity of [N-benzyltyr1]dynorphin A-(1-11) analogues. J. Med. Chem. 52, 6814-6821 (2009).
26. Binder W. Walker JS. Effect of the peripherally selective β-opioid agonist, asimadoline, on adjuvant arthritis. Br. J. Pharmacol. 124, 647-654 (1998). (Pubitemid 28276800)
27. Stevenson GW, Folk JE, Linsenmayer DC et al. Opioid interactions in rhesus monkeys: effects of d + μ and d + k agonists on schedule-controlled responding and thermal nociception. J. Pharm. Exp. Therap. 307, 1054-1064 (2003). (Pubitemid 37494225)
28. Roth BL, Baner K, Westkaemper R et al. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc. Natl Acad. Sci. USA 99, 11934-11939 (2002). (Pubitemid 34994502)
29. Aldrich JV, McLaughlin JP. Peptide kappa opioid receptor ligands: potential for drug development. AAPS J. 11, 312-322 (2009).
30. Yamada H, Shimoyama N, Sora I et al. Morphine can produce analgesia via spinal kappa opioid receptors in the absence of mu opioid receptors. Brain Res. 1083, 61-69 (2006).
31. Giardina G, Clarke GD, Grugni M et al. Central and peripheral analgesic agents: chemical strategies for limiting brain penetration in kappa-opioid agonists belonging to different chemical classes. Farmaco 50, 405-418 (1995).
32. Carroll I, Thomas JB, Dykstra LA et al. Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. Eur. J. Pharmacol. 501, 111-9 (2004). (Pubitemid 39298943)
33. Hökfelt T, Bartfai T, Bloom F. Neuropeptides: opportunities for drug discovery. Lancet Neurology 2, 463-472 (2003). (Pubitemid 36876103)
34. Cahill CM, Morinville A, Hoffert C et al. Up-regulation and trafficking of (opioid receptor in a model of chronic inflammation: implications for pain control. Pain 101, 199-208 (2003). (Pubitemid 36044668)
35. Weber E, Escht FS, Bohlen P et al. Metorphamide: isolation, structure, and biologic activity of an amidated opioid octapeptide from bovine brain. Proc. Natl Acad. Sci. USA 80, 7362-7366 (1983). (Pubitemid 14208858)
36. Arakawa K, De Jong W, Mulder AH et al. The electrically stimulated release of [3H] noradrenaline from nucleus tractus solitarii slices in vitro is modulated via β-opioid receptors. Eur. J. Pharm. 192, 311-316 (1991).
37. Ronken E, Wiegant VM, Kaspersen FM et al. Topography and characteristics of specific binding sites for non-opioid β-type endorphins in the rat brain as studied by autoradiography with [35S]Met-desenkephalin-g-endorphin. Brain Res. 615, 63-70 (1993). (Pubitemid 23189621)
38. Navolotskaya E, Kovalitskaya YA, Zolotarev YA et al. Binding of synthetic fragments of β-endorphin to nonopioid β-endorphin receptor. J. Peptide Sci. 14, 1121-1128 (2008).
39. Schwyzer R, Sargent DF. Membrane lipid phase as catalyst for peptide receptor interactions. Proc. Natl Acad. Sci. USA 83, 5774-78 (1986). (Pubitemid 16000594)
40. Tamm LK. Protein-Lipid Interactions. From Membrane Domains to Cellular Networks. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany (2005).
41. Adam G, Delbrück M. In: Structural Chemistry and Molecular Biology. Rich R, Davidson N (Eds). Freeman & Co., San Francisco, CA, USA, 198-199 (1968).
42. Saffman PG, Delbrück M. Brownian motion in biological membranes. Proc. Natl Acad. Sci. USA 72, 3111-3113 (1975).
43. Segrest JP, Jackson RL, Morrisett JD et al. A molecular theory of lipid-protein interactions in the plasma lipoproteins. FEBS Lett. 38, 247-253 (1974).
44. Epand RM, Shai Y, Segrest JP et al. Mechanisms for the modulation of membrane bilayer properties by amphipathic helical peptides. Biopolymers 37, 319-338 (1995).
45. Pardridge WM. The blood-brain barrier: bottleneck in brain drug development. NeuroRx: J. Am. Soc. Exp. NeuroTher. 2, 3-14 (2005). (Pubitemid 40128022)
46. Terasaki T, Hirai K, Sato H et al. Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078 into the blood-brain barrier. J. Pharm. Exp. Ther. 251, 351-357 (1989). (Pubitemid 19261986)
47. Deguchi Y, Miyakawa Y, Sakurada S et al. Blood-brain barrier transport of a novel micro 1-specific opioid peptide, H-Tyr-d- Arg-Phe-beta-Ala-OH (TAPA). J. Neurochem. 84, 1154-1161 (2003). (Pubitemid 36330667)
48. Kastin AJ, Pan W, Maness LM et al. Peptides crossing the blood-brain barrier: some unusual observations. Brain Res. 848, 96-100 (1999). (Pubitemid 30001658)
49. Bredeloux P, Cavelier F, Dubuc I et al. Synthesis and biological effects of c(Lys-Lys- Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012), a new analogue of neurotensin that crosses the blood-brain barrier. J. Med. Chem. 51, 1610-1616 (2008). (Pubitemid 351438845)
50. Egleton RD, Davis P. Development of neuropeptide drugs that cross the blood- brain barrier. NeuroRx: J. Am. Soc. Exp. NeuroTher. 2, 44-53 (2005). (Pubitemid 40128025)
51. Mehiri M, Chen W-H, Janout V et al. Molecular umbrella transport: exceptions to the classic size/lipophilicity rule. J. Am. Chem. Soc. 131, 1338-1339 (2009).
52. Pardridge WM. Re-engineering biopharmaceuticals for delivery to brain with molecular Trojan horses. Bioconjugate Chem. 19, 1327-1338 (2008). (Pubitemid 352032329)
53. Malakoutikhah M, Teixidó M, Giralt E. Toward an optimal blood-brain barrier shuttle by synthesis and evaluation of peptide libraries. J. Med. Chem. 51, 4881-4889 (2008).
54. Meldal M, Hilaire PM. Synthetic methods of glycopeptide assembly and biological analysis of glycopeptide products. Curr. Opin. Chem. Biol. 1, 552-563 (1997). (Pubitemid 127437857)
55. Boons GJ, Polt R. The chemistry of O- and N-linked glycopeptides. In: Carbohydrate Chemistry. Blackie Press, London, UK, 223-242 (1998).
56. Eriko T, Yuko N, Yasuhiro K et al. Chemoenzymatic synthesis of a MUC1 glycopeptide carrying non-natural sialyl TF-beta O-glycan. Biosci. Biotech. Biochem. 70, 2515-2522 (2006).
57. Nianhuan Y, Gabriel F, Hamed M et al. Facile synthesis of glycosylated Fmoc amino acid building blocks assisted by microwave irradiation. Carbohydrate Res. 345, 2277-2281 (2010).
58. Polt R, Szabò LZ, Treiberg J et al. General methods for alpha-O-ser/thr or beta-O-ser/thr glycosides and glycopeptides. Solid-phase synthesis of O-glycosyl cyclic enkephalin analogues. J. Am. Chem. Soc. 114, 10249-58 (1992). (Pubitemid 23032646)
59. Mitchell SA, Pratt MR, Hruby VJ, Polt R. Solid-phase synthesis of O-linked glycopeptide analogues of enkephalin. J. Org. Chem. 66, 2327-42 (2001). (Pubitemid 32867427)
60. 2O to produce β-glycosides. J. Carbohydr. Chem. 29, 181-206 (2010).
61. Lefever MR, Szabò LZ, Anglin B et al. Glycosylation of β-amino acids by sugar acetate donors with InBr3. Minimally competent Lewis acids. Carbohydr. Res. 347 (2012) (In press).
62. Hruby VJ, Toth G, Gehring CA et al. Topographically designed analogues of [d-Pen2,d-Pen5]enkephalin. J. Med. Chem. 34, 1823-1830 (1991).
63. Mosberg HI, Hurst R, Hruby VJ et al. Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc. Natl Acad. Sci. USA 80, 5871-5874 (1983). (Pubitemid 14227575)
64. Weber SJ, Abbruscato TJ, Brownson EA et al. Assessment of an in vitro blood-brain barrier model using several [Met5]enkephalin opioid analogs. J. Pharm. Exp. Ther. 266, 1649-1655 (1993). (Pubitemid 24175817)
65. Rodriguez RE, Rodriguez FD, Sacristan MP et al. New glycosylpeptides with high antinociceptive activity. Neurosci. Lett. 101, 89-94 (1989). (Pubitemid 19137652)
66. Polt R, Porreca F, Szabò LZ et al. Glycopeptide enkephalin analogues produceanalgesia in mice: evidence for penetration of the blood-brain barrier. Proc. Natl Acad. Sci. USA 91, 7114-7118 (1994). (Pubitemid 24226813)
67. Egleton RD, Mitchell SA, Huber JD et al. Improved bioavailability to the brain of glycosylated Met-enkephalin analogs. Brain Res. 881, 37-46 (2000).
68. Zajac J-M, Gacel G, Petit F et al. Deltakephalin, Tyr-d-Thr-Gly-Phe-Leu- Thr : a new highly potent and fully specific agonist for opiate b-receptors. Biochem. Biophys. Res. Commun. 111, 390-397 (1983). (Pubitemid 13119225)
69. Bilsky EJ, Egleton RD, Mitchell SA et al. Enkephalin glycopeptide analogues produce analgesia with reduced dependence liability. J. Med. Chem. 43, 2586-2590 (2000). (Pubitemid 30437141)
70. Egleton RD, Mitchell SA, Huber JD et al. Improved blood-brain barrier penetration and enhanced analgesia of an opioid peptide by glycosylation. J. Pharm. Exp. Therap. 299, 967-972 (2001). (Pubitemid 33104967)
71. Horvat S. Opioid peptides and their glycoconjugates: structure-activity relationships. Curr. Med. Chem. - Central Nervous System Agents 1, 133-154 (2001).
72. Elmagbari NO, Egleton RD, Palian MM et al. Antinociceptive structure-activity studies with enkephalin-based opioid glycopeptides. J. Pharm. Exp. Therap. 311, 290-297 (2004). (Pubitemid 39287808)
73. Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain 64, 493-501 (1996). (Pubitemid 26180156)
74. Lowery JJ, Raymond TJ, Giuvelis D et al. In vivo characterization of MMP-2200, a mixed d/μ opioid agonist, in mice. J. Pharmacol. Exp. Ther. 336, 767-78 (2011).
75. Do Carmo GP, Polt R, Bilsky R et al. Behavioral pharmacology of the μ/ d opioid glycopeptide MMP2200 in Rhesus monkeys. J. Pharm. Exp. Therap. 326, 939-948 (2008).
76. Brainin-Mattos J, Smith ND, Malkmus S et al. Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist. Pain 122, 174-181 (2006).
77. Codd EE, Carson JR, Colburn RW et al. JNJ-20788560 [9-(8-azabicyclo[3.2. 1] oct-3-ylidene)-9H-xanthene-3-carboxylic acid diethylamide], a selective delta opioid receptor agonist, is a potent and efficacious antihyperalgesic agent that does not produce respiratory depression, pharmacologic tolerance, or physical dependence. J. Pharmacol. Exp. Ther.. 329, 241-51 (2009).
78. Otis V, Sarret P, Gendron L. Spinal activation of delta opioid receptors alleviates cancer-related bone pain. Neurosci. 183, 221-9 (2011).
79. Bilsky EJ, Calderon SN, Wang T et al. SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist. J. Pharmacol. Exp. Ther. 273, 359-66 (1995).
80. Bilsky EJ, Bernstein RN, Pasternak GW et al. Selective inhibition of [d-Ala2, Glu4] deltorphin antinociception by supraspinal, but not spinal, administration of an antisense oligodeoxynucleotide to an opioid delta receptor. Life Sci. 55, PL37-PL43 (1994).
81. Wild KD, McCormick J, Bilsky EJ et al. Antinociceptive actions of BW373U86 in the mouse. J. Pharmacol. Exp. Ther. 267, 858-865 (1993). (Pubitemid 23352548)
82. Kreil G, Barra D, Simmaco M et al. Deltorphin, a novel amphibian skin peptide with high selectivity and affinity for delta opioid receptors. Eur. J. Pharmacol. 162, 123-128 (1989). (Pubitemid 19074884)
83. Pradhan AA, Befort K, Nozaki C et al. The delta opioid receptor: an evolving target for the treatment of brain disorders. TIPS 32, 581-90 (2011).
84. Roemer D, Buescher HH, Hill RC et al. A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity. Nature 268, 547-549 (1977). (Pubitemid 8153908)
85. Handa BK, Land AC, Lord JA et al. Analogues of β-LPH61-64 possesing selective agonist activity at β-opiate receptors. Eur. J. Pharmacol. 70, 531-540 (1981). (Pubitemid 11152788)
86. Sargent DF, Schwyzer R. Membrane lipid phase as catalyst for peptide receptor interactions. Proc. Natl Acad. Sci. USA 83, 5774-5778 (1986). (Pubitemid 16000594)
87. Lowery JJ, Yeomans L, Keyari CM et al. Glycosylation improves the central effects of DAMGO. Chem. Biol. Drug Des. 69, 41-47 (2007). (Pubitemid 46277779)
88. Yeomans L, Muthu D, Lowery JJ et al. Phosphorylation of enkephalins: NMR and CD studies in aqueous and membrane-mimicking environments. Chem. Biol. Drug Des. 78, 749-56 (2011).
89. Egleton RD, Bilsky EJ, Tollin G et al. Biousian glycopeptides penetrate the blood-brain barrier. Tetrahedron Asymm. 16, 65-75 (2005). (Pubitemid 40127076)
90. Taylor JW, Miller RJ, Kaiser ET. Structural characterization of beta-endorphin through the design, synthesis, and study of model peptides. Mol. Pharm. 22, 657-666 (1982). (Pubitemid 13201824)
91. Kaiser ET, Kézdy FJ. Amphiphilic secondary structure: design of peptide hormones. Science 223, 249-255 (1984). (Pubitemid 14215784)
92. Palian MM, Boguslavsky VI, O'Brien DF et al. Glycopeptide-membrane interactions: glycosyl enkephalin analogues adopt turn conformations by NMR and CD in amphipathic media. J. Am. Chem. Soc. 125(19), 5823-5831 (2003). (Pubitemid 36592908)
93. Dhanasekaran M, Alves I, Yeomans L et al. Glycopeptides related to β-endorphin adopt helical amphipathic conformations in the presence of lipid bilayers. J. Am. Chem. Soc. 127, 5435-5448 (2005). (Pubitemid 40569855)
94. Neumann J, Couvineau A, Murail S et al. Class-B GPCR activation: is ligand helix-capping the key? TIBS 33, 314-319 (2008).
95. Gronenborn AM, Bovermann G, Clore GM. A 1H-NMR study of the solution conformation of secretin. Resonance assignment and secondary structure. FEBS Lett. 215, 88-94 (1987). (Pubitemid 17099144)
96. Neidigh JW, Fesinmeyer RM, Prickett KS et al. Exendin-4 and glucagon-like-peptide-1: NMR structural comparisons in the solution and micelle-associated states. Biochemistry 40, 13188-13200 (2001). (Pubitemid 33043533)
97. Sasaki K, Dockerill S, Adamiak DA et al. X-ray analysis of glucagon and its relationship to receptor binding. Nature 257, 751-757 (1975).
98. Jin L, Briggs Sl, Chandrasekhar S et al. Crystal structure of human parathyroid hormone 1-34 at 0.9-Å resolution. J. Biol. Chem. 275, 27238-27244 (2000).
99. Inooka H, Ohtaki T, Kitahara O et al. Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat. Struct. Biol. 8, 161-165 (2001). (Pubitemid 32116070)
100. Lefever MR. Design, synthesis and characterization of helical opioid glycopeptides and fluorescent derivatives including optimization of serine glycosylation utilizing sugar acetates. Ph.D. Dissertation, The University of Arizona, USA (2010).
101. Li Y. Design, synthesis, and characterization of helical opioid glycopeptide agonists: the study of the structure-activity relationship and transport of glycopeptides related to beta-endorphin and dynorphin. Ph.D. Dissertation, The University of Arizona, USA (2011).
102. Job GE, Kennedy RJ, Heitmann B et al. Temperature- and length-dependent energetics of formation for polyalanine helices in water: assignment of w(Ala)(n,T) and temperature-dependent CD ellipticity standards. J. Am. Chem. Soc. 128, 8227-8233 (2006). (Pubitemid 43967767)
103. Chin DH, Woody RW, Rohl CA et al. Circular dichroism spectra of short, fixed-nucleus alanine helices. Proc. Natl Acad. Sci. USA 99, 15416-15421 (2002). (Pubitemid 35403949)
104. Biondi B, Giannini E, Negri L et al. Opioid peptides: synthesis and biological activity of new endomorphin analogues. Int. J. Peptide Res. Therap. 12, 145-151 (2006). (Pubitemid 43881843)
105. Negri L, Lattanzi R, Tabacco F et al. Dermorphin and deltorphin glycosylated analogues: synthesis and antinociceptive activity after systemic administration. J. Med. Chem. 42, 400-404 (1999). (Pubitemid 29085100)
106. Biondi L, Filira F, Giannini E et al. Novel glycosylated [Lys7]-dermorphin analogues: synthesis, biological activity and conformational investigations. J. Pept. Sci. 13, 179-189 (2007). (Pubitemid 46421014)
107. Dangoor D, Biondi B, Gobbo M et al. Novel glycosylated VIP analogs: synthesis, biological activity, and metabolic stability. J. Pept. Sci. 14, 321-328 (2008). (Pubitemid 351385424)