Design, synthesis, conformational analysis, and biological activity of Cα¹-to-Cα⁶ 1,4- and 4,1-disubstituted 1H-[1,2,3]triazol-1-yl-bridged oxytocin analogues

References

• Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629–683.
   PubMed Web of Science ®Google Scholar
• Lippert TH, Mueck AO, Seeger H, Pfaff A. Effects of oxytocin outside pregnancy. Horm Res. 2003;60(6):262–271.
   PubMedGoogle Scholar
• Chibbar R, Miller FD, Mitchell BF. Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition. J Clin Invest. 1993;91(1):185–192.
   PubMed Web of Science ®Google Scholar
• Nicholson HD, Swann RW, Burford GD, Wathes DC, Porter DG, Pickering BT. Identification of oxytocin and vasopressin in the testis and in adrenal tissue. Regul Pept. 1984;8(2):141–146.
   PubMedGoogle Scholar
• Ohlsson B, Truedsson M, Djerf P, Sundler F. Oxytocin is expressed throughout the human gastrointestinal tract. Regul Pept. 2006;135(1-2):7–11.
   PubMedGoogle Scholar
• Gutkowska J, Jankowski M, Lambert C, Mukaddam-Daher S, Zingg HH, McCann SM. Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart. Proc Natl Acad Sci U S A. 1997;94(21):11704–11709.
   PubMed Web of Science ®Google Scholar
• Colaianni G, Sun L, Zaidi M, Zallone A. Oxytocin and bone. Am J Physiol Regul Integr Comp Physiol. 2014;307(8):R970–R977.
   PubMed Web of Science ®Google Scholar
• Blanks AM, Thornton S. The role of oxytocin in parturition. BJOG Int J Obstet. 2003;110(Suppl20):46–51.
   PubMedGoogle Scholar
• Monks DT, Palanisamy A. Oxytocin: at birth and beyond. A systematic review of the long-term effects of peripartum oxytocin. Anaesthesia. 2021;76(11):1526–1537.
   PubMed Web of Science ®Google Scholar
• Rash JA, Aguirre-Camacho A, Campbell TS. Oxytocin and pain: a systematic review and synthesis of findings. Clin J Pain. 2014;30(5):453–462.
   PubMed Web of Science ®Google Scholar
• Kim SH, Bennett PR, Terzidou V. Advances in the role of oxytocin receptors in human parturition. Mol Cell Endocrinol. 2017;449:56–63.
   PubMed Web of Science ®Google Scholar
• Erickson EN, Myatt L, Danoff JS, Krol KM, Connelly JJ. Oxytocin receptor DNA methylation is associated with exogenous oxytocin needs during parturition and postpartum hemorrhage. Commun Med. 2023;3(1):11.
   PubMedGoogle Scholar
• Kodama Y, Tanaka I, Sato T, Hori K, Gen S, Morise M, Matsubara D, Sato M, Sekido Y, Hashimoto N. Oxytocin receptor is a promising therapeutic target of malignant mesothelioma. Cancer Sci. 2021;112(9):3520–3532.
   PubMed Web of Science ®Google Scholar
• Liu H, Gruber CW, Alewood PF, Möller A, Muttenthaler M. The oxytocin receptor signalling system and breast cancer: a critical review. Oncogene. 2020;39(37):5917–5932.
   PubMed Web of Science ®Google Scholar
• Liwo A, Tempczyk A, Oldziej S, Shenderovich MD, Hruby VJ, Talluri S, Ciarkowski J, Kasprzykowski F, Lankiewicz L, Grzonka Z. Exploration of the conformational space of oxytocin and arginine-vasopressin using the electrostatically driven Monte Carlo and molecular dynamics methods. Biopolymers. 1998;38(2):157–175.
   Web of Science ®Google Scholar
• Carter CS, Kenkel WM, MacLean EL, Wilson SR, Perkeybile AM, Yee JR, Ferris CF, Nazarloo HP, Porges SW, Davis JM, et al. Is oxytocin “nature’s medicine”? Pharmacol Rev. 2020;72(4):829–861.
   PubMed Web of Science ®Google Scholar
• Polácek I, Krejcí I, Nesvadba H, Rudinger J. Action of (1,6-di-alanine)-oxytocin and (1,6-di-serine)-oxytocin on the rat uterus and mammary gland in vitro. Eur J Pharmacol. 1970;9(2):239–245.
   PubMed Web of Science ®Google Scholar
• Brewster AI, Hruby VJ, Spatola AF, Bovey FA. Carbon-13 nuclear magnetic resonance spectroscopy of oxytocin, related oligopeptides, and selected analogs. Biochemistry. 1973;12(8):1643–1649.
   PubMed Web of Science ®Google Scholar
• Gruber CW, Koehbach J, Muttenthaler M. Exploring bioactive peptides from natural sources for oxytocin and vasopressin drug discovery. Future Med Chem. 2012;4(14):1791–1798.
   PubMed Web of Science ®Google Scholar
• Kato T, Endo S, Fujiwara T, Nagayama K. Oxytocin solution structure changes upon protonation of the n-terminus in dimethyl sulfoxide. J Biomol NMR. 1993;3(6):653–673.
   PubMed Web of Science ®Google Scholar
• Brewster AI, Hruby VJ. 300-mhz nuclear magnetic resonance study of oxytocin aqueous solution: conformational implications. Proc Natl Acad Sci U S A. 1973;70(12):3806–3809.
   PubMed Web of Science ®Google Scholar
• Wood SP, Tickle IJ, Treharne AM, Pitts JE, Mascarenhas Y, Li JY, Husain J, Cooper S, Blundell TL, Hruby VJ. Crystal structure analysis of deamino-oxytocin: conformational flexibility and receptor binding. Science. 1986;232(4750):633–636.
   PubMed Web of Science ®Google Scholar
• Trivedi MV, Laurence JS, Siahaan TJ. The role of thiols and disulfides on protein stability. Curr Protein Pept Sci. 2009;10(6):614–625.
   PubMed Web of Science ®Google Scholar
• MacRaild CA, Illesinghe J, van Lierop BJ, Townsend AL, Chebib M, Livett BG, Robinson AJ, Norton RS. Structure and activity of (2,8)-dicarba-(3,12)-cystino alpha-imi, an alpha-conotoxin containing a nonreducible cystine analogue. J Med Chem. 2009;52(3):755–762.
   PubMed Web of Science ®Google Scholar
• Yamanaka T, Hase S, Sakakibara S, Schwartz IL, Dubois BM, Walter R. Crystalline deamino-dicarba-oxytocin. Preparation and some pharmacological properties. Mol Pharmacol. 1970;6(5):474–480.
   PubMed Web of Science ®Google Scholar
• Stymiest JL, Mitchell BF, Wong S, Vederas JC. Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability. J Org Chem. 2005;70(20):7799–7809.
   PubMed Web of Science ®Google Scholar
• Bondebjerg J, Grunnet M, Jespersen T, Meldal M. Solid-phase synthesis and biological activity of a thioether analogue of conotoxin g1. Chembiochem. 2003;4(2-3):186–194.
   PubMed Web of Science ®Google Scholar
• Osapay G, Prokai L, Kim HS, Medzihradszky KF, Coy DH, Liapakis G, Reisine T, Melacini G, Zhu Q, Wang SH, et al. Lanthionine-somatostatin analogs: synthesis, characterization, biological activity, and enzymatic stability studies. J Med Chem. 1997;40(14):2241–2251.
   PubMed Web of Science ®Google Scholar
• Schramme AR, Pinto CR, Davis J, Whisnant CS, Whitacre MD. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, following intravenous administration in horses. Equine Vet J. 2008;40(7):658–661.
   PubMed Web of Science ®Google Scholar
• Sweeney G, Holbrook AM, Levine M, Yip M, Alfredsson K, Cappi S, Ohlin M, Schulz P, Wassenaar W. Pharmacokinetics of carbetocin, a long-acting oxytocin analog, in nonpregnant women. Curr Ther Res. 1990;47(3):528–540.
   Web of Science ®Google Scholar
• Muttenthaler M, Nevin ST, Grishin AA, Ngo ST, Choy PT, Daly NL, Hu SH, Armishaw CJ, Wang CI, Lewis RJ, et al. Solving the alpha-conotoxin folding problem: efficient selenium-directed on-resin generation of more potent and stable nicotinic acetylcholine receptor antagonists. J Am Chem Soc. 2010;132(10):3514–3522.
   PubMed Web of Science ®Google Scholar
• Walewska A, Zhang MM, Skalicky JJ, Yoshikami D, Olivera BM, Bulaj G. Integrated oxidative folding of cysteine/selenocysteine containing peptides: improving chemical synthesis of conotoxins. Angew Chem Int Ed Engl. 2009;48(12):2221–2224.
   PubMed Web of Science ®Google Scholar
• Gowd KH, Yarotskyy V, Elmslie KS, Skalicky JJ, Olivera M, Bulaj G. Site-specific effects of diselenide bridges on the oxidative folding of a cystine knot peptide, omega-selenoconotoxin GVIA. Biochemistry. 2010;49(12):2741–2752.
   PubMed Web of Science ®Google Scholar
• Metanis N, Keinan E, Dawson PE. Synthetic seleno-glutaredoxin 3 analogues are highly reducing oxidoreductases with enhanced catalytic efficiency. J Am Chem Soc. 2006;128(51):16684–16691.
   PubMed Web of Science ®Google Scholar
• Armishaw CJ, Daly NL, Nevin ST, Adams DJ, Craik DJ, Alewood PF. Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists. J Biol Chem. 2006;281(20):14136–14143.
   PubMed Web of Science ®Google Scholar
• Fiori S, Pegoraro S, Rudolph-Böhner S, Cramer J, Moroder L. Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities. Biopolymers. 2000;53(7):550–564.
   PubMed Web of Science ®Google Scholar
• Pegoraro S, Fiori S, Rudolph-Böhner S, Watanabe TX, Moroder L. Isomorphous replacement of cystine with selenocystine in endothelin: oxidative refolding, biological and conformational properties of [Sec3, Sec11, Nle7]-endothelin-1. J Mol Biol. 1998;284(3):779–792.
   PubMed Web of Science ®Google Scholar
• Muttenthaler M, Alewood PF. Selenopeptide chemistry. J Pept Sci. 2008;14(12):1223–1239.
   PubMed Web of Science ®Google Scholar
• Muttenthaler M, Andersson A, de Araujo AD, Dekan Z, Lewis RJ, Alewood PF. Modulating oxytocin activity and plasma stability by disulfide bond engineering. J Med Chem. 2010;53(24):8585–8596.
   PubMed Web of Science ®Google Scholar
• Dekan Z, Kremsmayr T, Keov P, Godin M, Teakle N, Dürrauer L, Xiang H, Gharib D, Bergmayr C, Hellinger R, et al. Nature-inspired dimerization as a strategy to modulate neuropeptide pharmacology exemplified with vasopressin and oxytocin. Chem Sci. 2021;12(11):4057–4062.
   PubMed Web of Science ®Google Scholar
• Smith CW, Walter R, Moore S, Makofske RC, Meienhofer J. Replacement of the disulfide bond in oxytocin by an amide group. Synthesis and some biological properties of (cyclo-(1-l-aspartic acid,6-l-alpha,beta-diaminopropionic acid))oxytocin. J Med Chem. 1978;21(1):117–120.
   PubMed Web of Science ®Google Scholar
• Hunter DJ, Schulz P, Wassenaar W. Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin Pharmacol Ther. 1992;52(1):60–67.
   PubMed Web of Science ®Google Scholar
• de Araujo AD, Mobli M, Castro J, Harrington AM, Vetter I, Dekan Z, Muttenthaler M, Wan J, Lewis RJ, King GF, et al. Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain. Nat Commun. 2014;5(1):3165.
   PubMedGoogle Scholar
• Moroder L. Isosteric replacement of sulfur with other chalcogens in peptides and proteins. J Pept Sci. 2005;11(4):187–214.
   PubMed Web of Science ®Google Scholar
• Roice M, Johannsen I, Meldal M. High capacity poly(ethylene glycol) based amino polymers for peptide and organic synthesis. QSAR Comb Sci. 2004;23(8):662–673.
   Google Scholar
• Rečnik LM, Kandioller W, Mindt TL. 1,4-disubstituted 1,2,3-triazoles as amide bond surrogates for the stabilisation of linear peptides with biological activity. Molecules. 2020;25(16):3576.
   PubMed Web of Science ®Google Scholar
• Testa C, Papini AM, Chorev M, Rovero P. Copper-catalyzed azide-alkyne cycloaddition (CuAAC)-mediated macrocyclization of peptides: impact on conformation and biological activity. Curr Top Med Chem. 2018;18(7):591–610.
   PubMed Web of Science ®Google Scholar
• Jiang X, Hao X, Jing L, Wu G, Kang D, Liu X, Zhan P. Recent applications of click chemistry in drug discovery. Expert Opin Drug Discov. 2019;14(8):779–789.
   PubMed Web of Science ®Google Scholar
• Horne WS, Stout CD, Ghadiri MR. A heterocyclic peptide nanotube. J Am Chem Soc. 2003;125(31):9372–9376.
   PubMed Web of Science ®Google Scholar
• Tornøe CW, Christensen C, Meldal M. Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem. 2002;67(9):3057–3064.
   PubMed Web of Science ®Google Scholar
• Holland-Nell K, Meldal M. Maintaining biological activity by using triazoles as disulfide bond mimetics. Angew Chem Int Ed Engl. 2011;50(22):5204–5206.
   PubMed Web of Science ®Google Scholar
• D’Ercole A, Sabatino G, Pacini L, Impresari E, Capecchi I, Papini AM, Rovero P. On-resin microwave-assisted copper-catalyzed azide-alkyne cycloaddition of h1-relaxin b single chain ‘stapled’ analogues. Pept Sci . 2020;112(4):1–10.
   Web of Science ®Google Scholar
• Cantel S, Le Chevalier Isaad A, Scrima M, Levy JJ, DiMarchi RD, Rovero P, Halperin JA, D'Ursi AM, Papini AM, Chorev M. Synthesis and conformational analysis of a cyclic peptide obtained via i to i + 4 intramolecular side-chain to side-chain azide-alkyne 1,3-dipolar cycloaddition. J Org Chem. 2008;73(15):5663–5674.
   PubMed Web of Science ®Google Scholar
• Castro V, Rodríguez H, Albericio F. CuAAC: an efficient click chemistry reaction on solid phase. ACS Comb Sci. 2016;18(1):1–14.
   PubMed Web of Science ®Google Scholar
• Scrima M, Grimaldi M, Di Marino S, Testa C, Rovero P, Papini AM, Chorev M, D'Ursi AM. Solvent independent conformational propensities of [1,2,3]triazolyl-bridged parathyroid hormone-related peptide-derived cyclo-nonapeptide analogues. Biopolymers. 2012;98(6):535–545.
   PubMed Web of Science ®Google Scholar
• Testa C, Scrima M, Grimaldi M, D'Ursi AM, Dirain ML, Lubin-Germain N, Singh A, Haskell-Luevano C, Chorev M, Rovero P, et al. 1,4-disubstituted-[1,2,3]triazolyl-containing analogues of MT-II: design, synthesis, conformational analysis, and biological activity. J Med Chem. 2014;57(22):9424–9434.
   PubMed Web of Science ®Google Scholar
• Testa C, D'Addona D, Scrima M, Tedeschi AM, D'Ursi AM, Bernhard C, Denat F, Bello C, Rovero P, Chorev M, et al. Design, synthesis, and conformational studies of [dota]-octreotide analogs containing [1,2,3]triazolyl as a disulfide mimetic. Pept Sci . 2018;110(5):e24071.
   Web of Science ®Google Scholar
• Le Chevalier Isaad A, Barbetti F, Rovero P, D'Ursi AM, Chelli M, Chorev M, Papini AM. Nα-Fmoc-protected ω-azido- and ω-alkynyl-l-amino acids as building blocks for the synthesis of “clickable” peptides. Eur J Org Chem. 2008;2008(31):5308–5314.
   Web of Science ®Google Scholar
• Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed. 2002;41(14):2596–2599.
   PubMed Web of Science ®Google Scholar
• Di Giglio MG, Muttenthaler M, Harpsøe K, Liutkeviciute Z, Keov P, Eder T, Rattei T, Arrowsmith S, Wray S, Marek A, et al. Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide. Sci Rep. 2017;7(1):41002.
   PubMedGoogle Scholar
• Koehbach J, O'Brien M, Muttenthaler M, Miazzo M, Akcan M, Elliott AG, Daly NL, Harvey PJ, Arrowsmith S, Gunasekera S, et al. Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design. Proc Natl Acad Sci U S A. 2013;110(52):21183–21188.
   PubMed Web of Science ®Google Scholar
• Rogi T, Tsujimoto M, Nakazato H, Mizutani S, Tomoda Y. Human placental leucine aminopeptidase/oxytocinase. A new member of type II membrane-spanning zinc metallopeptidase family. J Biol Chem. 1996;271(1):56–61.
   PubMed Web of Science ®Google Scholar
• Yamahara N, Nomura S, Suzuki T, Itakura A, Ito M, Okamoto T, Tsujimoto M, Nakazato H, Mizutani S. Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy. Life Sci. 2000;66(15):1401–1410.
   PubMed Web of Science ®Google Scholar
• Kobayashi H, Nomura S, Mitsui T, Ito T, Kuno N, Ohno Y, Kadomatsu K, Muramatsu T, Nagasaka T, Mizutani S. Tissue distribution of placental leucine aminopeptidase/oxytocinase during mouse pregnancy. J Histochem Cytochem. 2004;52(1):113–121.
   PubMed Web of Science ®Google Scholar
• Mohan S, McCloskey AG, McKillop AM, Flatt PR, Irwin N, Moffett RC. Development and characterisation of novel, enzymatically stable oxytocin analogues with beneficial antidiabetic effects in high fat fed mice. Biochim Biophys Acta Gen Subj. 2021;1865(3):129811.
   PubMed Web of Science ®Google Scholar
• Perczel A, Kollat E, Hollosi M, Fasman GD. Synthesis and conformational analysis of N-glycopeptides. II. CD, molecular dynamics and NMR spectroscopic studies on linear N-glycopeptides. Biopolymers. 1993;33(4):665–685.
   PubMed Web of Science ®Google Scholar
• Perczel A, Hollosi M. Turns. In: Fasman GD, editor. Circular dichroism and the conformational analysis of biomolecules. New York (NY): Plenum Press; 1996. p. 285–380.
   Google Scholar
• Waltenspühl Y, Ehrenmann J, Vacca S, Thom C, Medalia O, Plückthun A. Structural basis for the activation and ligand recognition of the human oxytocin receptor. Nat Commun. 2022;13(1):4153.
   PubMed Web of Science ®Google Scholar
• Meyerowitz JG, Robertson MJ, Barros-Álvarez X, Panova O, Nwokonko RM, Gao Y, Skiniotis G. The oxytocin signaling complex reveals a molecular switch for cation dependence. Nat Struct Mol Biol. 2022;29(3):274–281.
   PubMed Web of Science ®Google Scholar
• Lee W, Tonelli M, Markley JL. Nmrfam-sparky: enhanced software for biomolecular NMR spectroscopy. Bioinformatics. 2015;31(8):1325–1327.
   PubMed Web of Science ®Google Scholar
• Wishart DS, Bigam CG, Holm A, Hodges RS, Sykes BD. 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investigations of nearest-neighbor effects. J Biomol NMR. 1995;5(1):67–81.
   PubMed Web of Science ®Google Scholar
• Vuister GW, Bax A. Quantitative j correlation: a new approach for measuring homonuclear three-bond J(HNHα) coupling constants in 15N -enriched proteins. J Am Chem Soc. 1993;115(17):7772–7777.
   Web of Science ®Google Scholar
• Case DA, Babin V, Berryman JT, Betz RM, Cai Q, Cerutti DS, Cheatham TE, Darden TA, Duke RE, Gohlke H, et al. AMBER 14. San Francisco (CA): University of California. 2014.
   Google Scholar
• Jakalian A, Jack DB, Bayly CI. Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J Comput Chem. 2002;23(16):1623–1641.
   PubMed Web of Science ®Google Scholar
• Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C. ff14sb: improving the accuracy of protein side chain and backbone parameters from ff99sb. J Chem Theory Comput. 2015;11(8):3696–3713.
   PubMed Web of Science ®Google Scholar
• Byrne C, Belnou M, Baulieu E-E, Lequin O, Jacquot Y. Electronic circular dichroism and nuclear magnetic resonance studies of peptides derived from the fkbp52-interacting β-turn of the hERα ligand-binding domain. Pept Sci. 2019;111(4):1–14.
   Web of Science ®Google Scholar
• Waskom ML. Seaborn: statistical data visualization. J Open Source Softw. 2021;6(60):3021.
   Google Scholar
• Duerrauer L, Muratspahić E, Gattringer J, Keov P, Mendel HC, Pfleger KDG, Muttenthaler M, Gruber CW. I8-arachnotocin-an arthropod-derived G protein-biased ligand of the human vasopressin V2 receptor. Sci Rep. 2019;9(1):19295.
   PubMedGoogle Scholar