Disulfide Bond Replacement with 1,4- and 1,5-Disubstituted [1,2,3]-Triazole on C-X-C Chemokine Receptor Type 4 (CXCR4) Peptide Ligands: Small Changes that Make Big Differences.


Journal

Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783

Informations de publication

Date de publication:
06 Aug 2020
Historique:
received: 19 05 2020
revised: 29 06 2020
pubmed: 1 7 2020
medline: 3 3 2021
entrez: 1 7 2020
Statut: ppublish

Résumé

Here we investigated the structural and biological effects ensuing from the disulfide bond replacement of a potent and selective C-X-C chemokine receptor type 4 (CXCR4) peptide antagonist, with 1,4- and 1,5- disubstituted 1,2,3-triazole moieties. Both strategies produced candidates that showed high affinity and selectivity against CXCR4. Notably, when assessed for their ability to modulate the CXCL12-mediated cell migration, the 1,4-triazole variant conserved the antagonistic effect in the low-mid nanomolar range, while the 1,5-triazole one displayed the ability to activate the migration, becoming the first in class low-molecular-weight CXCR4 peptide agonist. By combining NMR and computational studies, we provided a valuable model that highlighted differences in the interactions of the two peptidomimetics with the receptor that could account for their different functional profile. Finally, we envisage that our findings could be translated to different GPCR-interacting peptides for the pursuit of novel chemical probes that could assist in dissecting the complex puzzle of this fundamental class of transmembrane receptors.

Identifiants

pubmed: 32603023
doi: 10.1002/chem.202002468
doi:

Substances chimiques

Chemokine CXCL12 0
Disulfides 0
Ligands 0
Peptides 0
Peptidomimetics 0
Receptors, CXCR4 0
Triazoles 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

10113-10125

Subventions

Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 2017PHRC8X_004
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : AIM1873131 - 2, linea 1
Organisme : Regione Campania
ID : B61G18000470007

Informations de copyright

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Références

M. Góngora-Benítez, J. Tulla-Puche, F. Albericio, Chem. Rev. 2014, 114, 901-926.
 
Y. Liu, J. Biochem. 2004, 135, 1-6;
Z.-Y. Guo, X.-Y. Jia, Y.-M. Feng, Biol. Chem. 2004, 385, 1171-1175.
N. Morozumi, S. Sato, S. Yoshida, Y. Harada, M. Furuya, Y. Minamitake, K. Kangawa, Peptides 2017, 97, 16-21.
A. Jamil Sami, Curr. Protein Pept. Sci. 2007, 8, 283-292.
U. Kumar, S. Singh, Int. J. Mol. Sci. 2020, 21, 2568.
 
H. Nassour, M. Iddir, D. Chatenet, Trends Pharmacol. Sci. 2019, 40, 725-734;
F. Merlino, E. Billard, A. M. Yousif, S. Di Maro, D. Brancaccio, L. Abate, A. Carotenuto, R. Bellavita, R. d'Emmanuele di Villa Bianca, P. Santicioli, L. Marinelli, E. Novellino, T. E. Hébert, W. D. Lubell, D. Chatenet, P. Grieco, J. Med. Chem. 2019, 62, 1455-1467.
 
G. Barany, N. Kneib-Cordonier, D. G. Mullen, Int. J. Pept. Protein Res. 2009, 30, 705-739;
B. Mandal, B. Basu, RSC Adv. 2014, 4, 13854;
A. J. Mijalis, D. A. Thomas, M. D. Simon, A. Adamo, R. Beaumont, K. F. Jensen, B. L. Pentelute, Nat. Chem. Biol. 2017, 13, 464-466;
S. K. Singh, J. M. Collins, Meth. Mol. Biol. 2019, 95-109.
K. K. Khoo, R. S. Norton, in Amino Acids, Peptides and Proteins in Organic Chemistry, Vol. 5 (Eds. A. B. Hughes), Wiley-VCH, Weinheim, 2011, 395-417.
N. Berger, F. Li, B. Mallick, J. T. Brüggemann, W. Sander, C. Merten, Biopolymers 2016, 107, 28-34.
A. M. Almeida, R. Li, S. H. Gellman, J. Am. Chem. Soc. 2012, 134, 75-78.
C. M. Santiveri, E. León, M. Rico, M. A. Jiménez, Chem. Eur. J. 2008, 14, 488-499.
A. Snellman, A. Tuomisto, A. Koski, A. Latvanlehto, T. Pihlajaniemi, J. Biol. Chem. 2007, 282, 14898-14905.
C. M. B. K. Kourra, N. Cramer, Chem. Sci. 2016, 7, 7007-7012.
 
B. Hargittai, N. A. Solé, D. R. Groebe, S. N. Abramson, G. Barany, J. Med. Chem. 2000, 43, 4787-4792;
P. Grieco, A. Carotenuto, R. Patacchini, C. A. Maggi, E. Novellino, P. Rovero, Bioorg. Med. Chem. 2002, 10, 3731-3739.
 
D. D'Addona, A. Carotenuto, E. Novellino, V. Piccand, J. C. Reubi, A. D. Cianni, F. Gori, A. M. Papini, M. Ginanneschi, J. Med. Chem. 2008, 51, 512-520;
P. Martín-Gago, R. Ramón, E. Aragón, J. Fernández-Carneado, P. Martin-Malpartida, X. Verdaguer, P. López-Ruiz, B. Colás, M. A. Cortes, B. Ponsati, M. J. Macias, A. Riera, Bioorg. Med. Chem. Lett. 2014, 24, 103-107;
S. Chhabra, A. Belgi, P. Bartels, B. J. V. Lierop, S. D. Robinson, S. N. Kompella, A. Hung, B. P. Callaghan, D. J. Adams, A. J. Robinson, R. S. Norton, J. Med. Chem. 2014, 57, 9933-9944.
 
P. J. Knerr, A. Tzekou, D. Ricklin, H. Qu, H. Chen, W. A. V. D. Donk, J. D. Lambris, ACS Chem. Biol. 2011, 6, 753-760;
K. Pulka-Ziach, V. Pavet, N. Chekkat, K. Estieu-Gionnet, R. Rohac, M.-C. Lechner, C. R. Smulski, G. Zeder-Lutz, D. Altschuh, H. Gronemeyer, S. Fournel, B. Odaert, ChemBioChem 2014, 16, 293-301.
 
S. Fiori, S. Pegoraro, S. Rudolph-Böhner, J. Cramer, L. Moroder, Biopolymers 2000, 53, 550-564;
C. J. Armishaw, N. L. Daly, S. T. Nevin, D. J. Adams, D. J. Craik, P. F. Alewood, J. Biol. Chem. 2006, 281, 14136-14143;
K. Arai, T. Takei, M. Okumura, S. Watanabe, Y. Amagai, Y. Asahina, L. Moroder, H. Hojo, K. Inaba, M. Iwaoka, Angew. Chem. Int. Ed. 2017, 56, 5522-5526;
Angew. Chem. 2017, 129, 5614-5618.
 
K. Holland-Nell, M. Meldal, Angew. Chem. Int. Ed. 2011, 50, 5204-5206;
Angew. Chem. 2011, 123, 5310-5312;
M. Empting, O. Avrutina, R. Meusinger, S. Fabritz, M. Reinwarth, M. Biesalski, S. Voigt, G. Buntkowsky, H. Kolmar, Angew. Chem. Int. Ed. 2011, 50, 5207-5211;
Angew. Chem. 2011, 123, 5313-5317;
A. White, S. D. Veer, G. Wu, P. Harvey, K. Yap, G. J. King, J. E. Swedberg, C. K. Wang, R. H. P. Law, T. Durek, D. Craik, Angew. Chem. Int. Ed. 2020, 59, 11273-11277;
Angew. Chem. 2020, 132, 11369-11373.
 
S. Cantel, A. L. C. Isaad, M. Scrima, J. J. Levy, R. D. Dimarchi, P. Rovero, J. A. Halperin, A. M. D'Ursi, A. M. Papini, M. Chorev, J. Org. Chem. 2008, 73, 5663-5674;
A. A. Rashad, Methods Mol. Biol. 2001, 133-145;
A. Knuhtsen, C. Whitmore, F. S. Mcwhinnie, L. Mcdougall, R. Whiting, B. O. Smith, C. M. Timperley, A. C. Green, K. I. Kinnear, A. G. Jamieson, Chem. Sci.. 2019, 10, 1671-1676.
 
A. Dondoni, P. P. Giovannini, A. Massi, Org. Lett. 2004, 6, 2929-2932;
Q. Wan, J. Chen, G. Chen, S. J. Danishefsky, J. Org. Chem. 2006, 71, 8244-8249;
N. Miller, G. M. Williams, M. A. Brimble, Org. Lett. 2010, 12, 1375-1376;
N. G. Quigley, S. Tomassi, F. S. Di Leva, S. Di Maro, F. Richter, K. Steiger, S. Kossatz, L. Marinelli, J. Notni, ChemBioChem 2020, https://doi.org/10.1002/cbic.202000200.
S. R. Tala, A. Singh, C. J. Lensing, S. M. Schnell, K. T. Freeman, J. R. Rocca, C. Haskell-Luevano, ACS Chem. Neurosci. 2018, 9, 1001-1013.
S. Pacifico, A. Kerckhoffs, A. J. Fallow, R. E. Foreman, R. Guerrini, J. Mcdonald, D. G. Lambert, A. G. Jamieson, Org. Biomol. Chem. 2017, 15, 4704-4710.
J. A. Burger, T. J. Kipps, Blood 2006, 107, 1761-1767.
J. F. Berson, D. Long, B. J. Doranz, J. Rucker, F. R. Jirik, R. W. Doms, J. Virol. 1996, 70, 6288-6295.
S. Chatterjee, B. B. Azad, S. Nimmagadda, Adv. Cancer Res. Emerging Applications of Molecular Imaging to Oncology 2014, 124, 31-82.
M. R. Kuhne, T. Mulvey, B. Belanger, S. Chen, C. Pan, C. Chong, F. Cao, W. Niekro, T. Kempe, K. A. Henning, L. J. Cohen, A. J. Korman, P. M. Cardarelli, Clin. Cancer Res. 2013, 19, 357-366.
F. Grande, G. Giancotti, G. Ioele, M. A. Occhiuzzi, A. Garofalo, Eur. J. Med. Chem. 2017, 139, 519-530.
D. Karpova, S. Bräuninger, E. Wiercinska, A. Krämer, B. Stock, J. Graff, H. Martin, A. Wach, C. Escot, G. Douglas, B. Romagnoli, E. Chevalier, K. Dembowski, L. Hooftman, H. Bonig, J. Trans. Med. 2017, 15, 2.
 
L. M. Pelus, H. Bian, S. Fukuda, D. Wong, A. Merzouk, H. Salari, Exp. Hematol. 2005, 33, 295-307;
W.-T. Choi, S. Duggineni, Y. Xu, Z. Huang, J. An, J. Med. Chem. 2012, 55, 977-994;
J. Quoyer, J. M. Janz, J. Luo, Y. Ren, S. Armando, V. Lukashova, J. L. Benovic, K. E. Carlson, S. W. Hunt, M. Bouvier, Proc. Natl. Acad. Sci. USA 2013, 110, E5088-E5097;
R. K. Mishra, A. K. Shum, L. C. Platanias, R. J. Miller, G. E. Schiltz, Sci. Rep. 2016, 6, 30155.
 
M. Lefrançois, M.-R. Lefebvre, G. Saint-Onge, P. E. Boulais, S. Lamothe, R. Leduc, P. Lavigne, N. Heveker, E. Escher, ACS Med. Chem. Lett. 2011, 2, 597-602;
C. E. Mona, É. Besserer-Offroy, J. Cabana, M. Lefrançois, P. E. Boulais, M.-R. Lefebvre, R. Leduc, P. Lavigne, N. Heveker, É. Marsault, E. Escher, J. Med. Chem. 2016, 59, 7512-7524.
L. Portella, R. Vitale, S. D. Luca, C. D'Alterio, C. Ieranò, M. Napolitano, A. Riccio, M. N. Polimeno, L. Monfregola, A. Barbieri, A. Luciano, A. Ciarmiello, C. Arra, G. Castello, P. Amodeo, S. Scala, PLoS ONE 2013, 8, e74548.
 
S. Di Maro, A. M. Trotta, D. Brancaccio, F. S. Di Leva, V. La Pietra, C. Ieranò, M. Napolitano, L. Portella, C. D'Alterio, R. A. Siciliano, D. Sementa, S. Tomassi, A. Carotenuto, E. Novellino, S. Scala, L. Marinelli, J. Med. Chem. 2016, 59, 8369-8380;
S. Di Maro, F. S. Di Leva, A. M. Trotta, D. Brancaccio, L. Portella, M. Aurilio, S. Tomassi, A. Messere, D. Sementa, S. Lastoria, A. Carotenuto, E. Novellino, S. Scala, L. Marinelli, J. Med. Chem. 2017, 60, 9641-9652;
S. Santagata, M. Napolitano, C. Dalterio, S. Desicato, S. Di Maro, L. Marinelli, A. Fragale, M. Buoncervello, F. Persico, L. Gabriele, E. Novellino, N. Longo, S. Pignata, S. Perdonà, S.a Scala, Oncotarget 2017, 8, 77110-77120;
D. Brancaccio, D. Diana, S. Di Maro, F. S. Di Leva, S. Tomassi, R. Fattorusso, L. Russo, S. Scala, A. M. Trotta, L. Portella, E. Novellino, L. Marinelli, A. Carotenuto, J. Med. Chem. 2018, 61, 2910-2923.
F. Merlino, S. Tomassi, A. M. Yousif, A. Messere, L. Marinelli, P. Grieco, E. Novellino, S. Cosconati, S. Di Maro, Org. Lett. 2019, 21, 6378-6382.
 
C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057-3064;
J. M. Holub, H. Jang, H. Kirshenbaum, Org. Biomol. Chem. 2006, 4, 1497-1502.
M. Wrobel, J. Aubé, B. König, Beilstein J. Org. Chem. 2012, 8, 1027-1036.
K. Wütrich, NMR of Proteins and Nucleic Acids, John Wiley & Sons, Inc: New York.
 
U. Piantini, O. W. Sorensen, R. R. Ernst, J. Am. Chem. Soc. 1982, 104, 6800-6801;
D. Marion, K. Wüthrich, Biochem. Biophys. Res. Commun. 1983, 113, 967-974.
L. Braunschweiler, R. R. Ernst, J. Magn. Reson. 1983, 53, 521-528.
J. Jeener, B. H. Meyer, P. Bachman, R. R. Ernst, J. Chem. Phys. 1979, 71, 4546-4553.
 
M. Arimont, S. L. Sun, R. Leurs, M. Smit, I. J. P. De Esch, C. De Graaf, J. Med. Chem. 2017, 60, 4735-4779;
B. Wu, E. Y. T. Chien, C. D. Mol, G. Fenalti, W. Liu, V. Katritch, R. Abagyan, A. Brooun, P. Wells, F. C. Bi, D. J. Hamel, P. Kuhn, T. M. Handel, V. Cherezov, R. C. Stevens, Science 2010, 330, 1066-1071;
S. Thiele, J. Mungalpara, A. Steen, M. M. Rosenkilde, J. Våbenø, Br. J. Pharmacol. 2014, 171, 5313-5329.
 
J. Mungalpara, S. Thiele, Ø. Eriksen, J. Eksteen, M. M. Rosenkilde, J. Våbenø, J. Med. Chem. 2012, 55, 10287-10291;
Z. G. Zachariassen, S. Karlshøj, B. E. Haug, M. M. Rosenkilde, J. Våbenø, J. Med. Chem. 2015, 58, 8141-8153.
A. Brelot, N. Heveker, M. Montes, M. Alizon, J. Biol. Chem. 2000, 275, 23736-23744.
E. W. Smith, A. M. Nevins, Z. Qiao, Y. Liu, A. E. Getschman, S. L. Vankayala, M. T. Kemp, F. C. Peterson, R. Li, B. F. Volkman, Y. Chen, J. Med. Chem. 2016, 59, 4342-4351.
 
M. P. Wescott, I. Kufareva, C. Paes, J. R. Goodman, Y. Thaker, B. A. Puffer, E. Berdougo, J. B. Rucker, T. M. Handel, B. J. Doranz, Proc. Natl. Acad. Sci. USA 2016, 113, 9928-9933;
J. J. Ziarek, A. B. Kleist, N. London, B. Raveh, N. Montpas, J. Bonneterre, G. St-Onge, C. J. DiCosmo-Ponticello, C. A. Koplinski, I. Roy, B. Stephens, S. Thelen, C. T. Veldkamp, F. D. Coffman, M. C. Cohen, M. B. Dwinell, M. Thelen, F. C. Peterson, N. Heveker, B. F. Volkman, Sci. Signaling 2017, 10, eaah5756.
D. J. States, R. A. Haberkorn, D. J. Ruben, J. Magn. Reson. 1982, 48, 286-292.
C. Bartels, T. Xia, M. Billeter, P. Guentert, K. Wüthrich, J. Biomol. NMR 1995, 6, 1-10.
P. Güntert, L. Buchner, J. Biomol. NMR 2015, 62, 453-471.
J. R. Maple, U. Dinur, A. T. Hagler, Proc. Natl. Acad. Sci. USA 1988, 85, 5350-5354.
E. F. Pettersen, T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, T. E. Ferrin, Comput. Chem. 2004, 25, 1605-1612.
G. Madhavi Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, J. Comput. Aided Mol. Des. 2013, 27, 221-234.
 
J. C. Shelley, A. Cholleti, L. L. Frye, J. R. Greenwood, M. R. Timlin, M. Uchimaya, J. Comput. Aided Mol. Des. 2007, 21, 681-691;
J. R. Greenwood, D. Calkins, A. P. Sullivan, J. C. Shelley, J. Comput. Aided Mol. Des. 2010, 24, 591-604.
 
R. A. Friesner, J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, M. P. Repasky, E. H. Knoll, M. Shelley, J. K. Perry, D. E. Shaw, P. Francis, P. S. Shenkin, J. Med. Chem. 2004, 47, 1739-1749;
T. A. Halgren, R. B. Murphy, R. A. Friesner, H. S. Beard, L. L. Frye, W. T. Pollard, J. L. Banks, J. Med. Chem. 2004, 47, 1750-1759.
E. Harder, W. Damm, J. Maple, C. Wu, M. Reboul, J. Y. Xiang, L. Wang, D. Lupyan, M. K. Dahlgren, J. L. Knight, J. W. Kaus, D. S. Cerutti, G. Krilov, W. L. Jorgensen, R. Abel, R. A. Friesner, J. Chem. Theory Comput. 2016, 12, 281-296.
 
M. P. Jacobson, R. A. Friesner, Z. Xiang, B. Honig, J. Mol. Biol. 2002, 320, 597-608;
M. P. Jacobson, D. L. Pincus, C. S. Rapp, T. J. F. Day, B. Honig, D. E. Shaw, R. A. Friesner, Proteins Struct. Funct. Bioinf. 2004, 55, 351-367.
J. A. Maier, C. Martinez, K. Kasavajhala, L. Wickstrom, K. E. Hauser, C. Simmerling, J. Chem. Theory Comput. 2015, 11, 3696-3713.
J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman, D. A. Case, J. Comput. Chem. 2004, 25, 1157-1174.
C. I. Bayly, P. Cieplak, W. D. Cornell, P. A. Kollman, J. Phys. Chem. 1993, 97, 10269-10280.
J. Wang, W. Wang, P. A. Kollman, D. A. Case, J. Mol. Graph. Model. 2006, 25, 247-260.
Gaussian 16, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. et al., Gaussian, Inc., Wallingford CT, 2016.
D. A. Case, I. Y. Ben-Shalom, S. R. Brozell, D. S. Cerutti, T. E. Cheatham III, V. W. D. Cruzeiro, T. A. Darden, R. E. Duke, D. Ghoreishi, M. K. Gilson, H. Gohlke, et al. 2018, AMBER 2018, University of California, San Francisco.
H. J. C. Berendsen, D. van der Spoel, R. van Drunen, Comput. Phys. Commun. 1995, 91, 43-56.
T. Darden, D. York, L. Pedersen, J. Chem. Phys. 1993, 98, 10089.
B. Hess, H. Bekker, H. J. C. Berendsen, J. G. E. M. Fraaije, J. Comput. Chem. 1997, 18, 1463-1472.
H. J. C. Berendsen, J. P. M. Postma, W. F. Van Gunsteren, A. Dinola, J. R. Haak, J. Chem. Phys. 1984, 81, 3684-3690.
G. Bussi, D. Donadio, M. Parrinello, J. Chem. Phys. 2007, 126, 014101.
M. Parrinello, A. Rahman, J. Appl. Phys. 1981, 52, 7182-7190.

Auteurs

Stefano Tomassi (S)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Anna Maria Trotta (AM)

U.O.C. "Bersagli molecolari del microambiente", Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Via M. Semmola, 80131, Naples, Italy.

Caterina Ieranò (C)

U.O.C. "Bersagli molecolari del microambiente", Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Via M. Semmola, 80131, Naples, Italy.

Francesco Merlino (F)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Anna Messere (A)

DiSTABiF, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy.

Giuseppina Rea (G)

U.O.C. "Bersagli molecolari del microambiente", Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Via M. Semmola, 80131, Naples, Italy.

Federica Santoro (F)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Diego Brancaccio (D)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Alfonso Carotenuto (A)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Vincenzo Maria D'Amore (VM)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Francesco Saverio Di Leva (FS)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Ettore Novellino (E)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Sandro Cosconati (S)

DiSTABiF, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy.

Luciana Marinelli (L)

Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.

Stefania Scala (S)

U.O.C. "Bersagli molecolari del microambiente", Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Via M. Semmola, 80131, Naples, Italy.

Salvatore Di Maro (S)

DiSTABiF, University of Campania "Luigi Vanvitelli", Via Vivaldi 43, 81100, Caserta, Italy.

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