Page 5 of 6
Journal of Medicinal Chemistry
(15) Yoshikawa, Y.; Kobayashi, K.; Oishi, S.; Fujii, N.; Furuya, T.
2ꢀNal, Lꢀ3ꢀ(2ꢀnaphthyl)ꢀalanine; Aib, 2ꢀaminoisobutyric acid;
Molecular Modeling Study of Cyclic Pentapeptide CXCR4
Antagonists: New Insight into CXCR4ꢀFC131 Interactions. Bioorg.
Med. Chem. Lett. 2012, 22, 2146ꢀ2150.
(16) Demmer, O.; Frank, A. O.; Hagn, F.; Schottelius, M.;
Marinelli, L.; Cosconati, S.; BrackꢀWerner, R.; Kremb, S.; Wester,
H.ꢀJ.; Kessler, H. A Conformationally Frozen Peptoid Boosts CXCR4
Affinity and AntiꢀHIV Activity. Angew. Chem. Int. Ed. Engl. 2012,
51, 8110ꢀ8113.
(17) Nikiforovich, G. V.; Kövér, K. E.; Zhang, W.ꢀJ.; Marshall, G.
R. Cyclopentapeptides as Flexible Conformational Templates. J. Am.
Chem. Soc. 2000, 122, 3262ꢀ3273.
(18) Bollhagen, R.; Schmiedberger, M.; Barlos, K.; Grell, E. A
New Reagent for the Cleavage of Fully Protected Peptides
Synthesised on 2ꢀChlorotrityl Chloride Resin. J. Chem. Soc., Chem.
Commun. 1994, 2559 ꢀ 2560.
(19) Kostenis, E.; Zeng, F. Y.; Wess, J. Functional Characterization
of a Series of Mutant G Protein αq Subunits Displaying Promiscuous
Receptor Coupling Properties. J. Biol. Chem. 1998, 273, 17886ꢀ
17892.
(20) Rosenkilde, M. M.; Gerlach, L.ꢀO.; Jakobsen, J. S.; Skerlj, R.
T.; Bridger, G. J.; Schwartz, T. W. Molecular Mechanism of
AMD3100 Antagonism in the CXCR4 Receptor: Transfer of Binding
Site to the CXCR3 Receptor. J. Biol. Chem. 2004, 279, 3033ꢀ3041.
(21) Rosenkilde, M. M.; Gerlach, L.ꢀO.; Hatse, S.; Skerlj, R. T.;
Schols, D.; Bridger, G. J.; Schwartz, T. W. Molecular Mechanism of
Action of Monocyclam Versus Bicyclam NonꢀPeptide Antagonists in
the CXCR4 Chemokine Receptor. J. Biol. Chem. 2007, 282, 27354ꢀ
27365.
(22) Jensen, P. C.; Thiele, S.; Ulven, T.; Schwartz, T. W.;
Rosenkilde, M. M. Positive Versus Negative Modulation of Different
Endogenous Chemokines for CCꢀChemokine Receptor 1 by Small
Molecule Agonists through Allosteric Versus Orthosteric Binding. J.
Biol. Chem. 2008, 283, 23121ꢀ23128.
(23) Thiele, S.; Steen, A.; Jensen, P. C.; Mokrosinski, J.; Frimurer,
T. M.; Rosenkilde, M. M. Allosteric and Orthosteric Sites in CC
Chemokine Receptor (CCR5), a Chimeric Receptor Approach. J.
Biol. Chem. 2011, 286, 37543ꢀ37554.
1
2
3
4
5
6
7
8
Aph, Lꢀ4ꢀaminoꢀphenylalanine; Api, 4ꢀaminopiperidineꢀ4ꢀ
carboxylic acid; Chx, 1ꢀaminocyclohexaneꢀ1ꢀcarboxylic acid; Cit,
Lꢀcitrulline; CXCL12, chemokine (CꢀXꢀC motif) ligand 12;
CXCR4, CꢀXꢀC chemokine receptor 4; DIPEA, N,Nꢀ
diisopropylethylamine; Gph, Lꢀ4ꢀguanidinoꢀphenylalanine; Gpi,
4ꢀaminoꢀ1ꢀcarbamimidoylpiperidineꢀ4ꢀcarboxylic acid; HBTU,
Oꢀ(benzotriazolꢀ1ꢀyl)ꢀN,N,N’,N’ꢀtetramethyluronium hexafluoroꢀ
phosphate; HFIP, 1,1,1,3,3,3ꢀhexafluoroꢀ2ꢀpropanol; Orn, Lꢀ
ornithine;
PyBOP,
(benzotriazolꢀ1ꢀ
9
yloxy)tripyrrolidinophosphonium hexafluorophosphate; TIS,
triisopropylsilane; Xaa, any amino acid.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
REFERENCES
(1) Murphy, P. M.; Baggiolini, M.; Charo, I. F.; Hebert, C. A.;
Horuk, R.; Matsushima, K.; Miller, L. H.; Oppenheim, J. J.; Power, C.
A. International Union of Pharmacology. XXII. Nomenclature for
Chemokine Receptors. Pharmacol. Rev. 2000, 52, 145ꢀ176.
(2) Feng, Y.; Broder, C. C.; Kennedy, P. E.; Berger, E. A. HIVꢀ1
Entry Cofactor: Functional cDNA Cloning of
a
Sevenꢀ
Transmembrane, G ProteinꢀCoupled Receptor. Science 1996, 272,
872ꢀ877.
(3) Berson, J. F.; Long, D.; Doranz, B. J.; Rucker, J.; Jirik, F. R.;
Doms, R. W. A SevenꢀTransmembrane Domain Receptor Involved in
Fusion and Entry of TꢀCellꢀTropic Human Immunodeficiency Virus
Type 1 Strains. J. Virol. 1996, 70, 6288ꢀ6295.
(4) Steen, A.; Rosenkilde, M. M. Molecular Pharmacology of
CXCR4 Inhibition. In Novel Developments in Stem Cell Mobilization:
Focus on CXCR4, Fruehauf, S.; Zeller, W. J.; Calandra, G., Eds.
Springer: 2012; pp 23ꢀ37.
(5) Balkwill, F. The Significance of Cancer Cell Expression of the
Chemokine Receptor CXCR4. Semin. Cancer Biol. 2004, 14, 171ꢀ
179.
(6) Singh, I. P.; Chauthe, S. K. Small Molecule HIV Entry
Inhibitors: Part I. Chemokine Receptor Antagonists: 2004 ꢀ 2010.
Expert Opin. Ther. Patents 2011, 21, 227ꢀ269.
(7) Choi, W. T.; Duggineni, S.; Xu, Y.; Huang, Z.; An, J. Drug
Discovery Research Targeting the CXC Chemokine Receptor 4
(CXCR4). J. Med. Chem. 2012, 55, 977ꢀ994.
(24) Tamamura, H.; Araki, T.; Ueda, S.; Wang, Z.; Oishi, S.;
Esaka, A.; Trent, J. O.; Nakashima, H.; Yamamoto, N.; Peiper, S. C.;
Otaka, A.; Fujii, N. Identification of Novel Low Molecular Weight
CXCR4 Antagonists by Structural Tuning of Cyclic Tetrapeptide
Scaffolds. J. Med. Chem. 2005, 48, 3280ꢀ3289.
(8) DiPersio, J. F.; Uy, G. L.; Yasothan, U.; Kirkpatrick, P.
Plerixafor. Nat. Rev. Drug Discov. 2009, 8, 105ꢀ107.
(9) Wu, B.; Chien, E. Y. T.; Mol, C. D.; Fenalti, G.; Liu, W.;
Katritch, V.; Abagyan, R.; Brooun, A.; Wells, P.; Bi, F. C.; Hamel, D.
J.; Kuhn, P.; Handel, T. M.; Cherezov, V.; Stevens, R. C. Structures
of the CXCR4 Chemokine GPCR with SmallꢀMolecule and Cyclic
Peptide Antagonists. Science 2010, 330, 1066ꢀ1071.
(10) Oishi, S.; Fujii, N. Peptide and Peptidomimetic Ligands for
CXC Chemokine Receptor 4 (CXCR4). Org. Biomol. Chem. 2012.
(11) Fujii, N.; Oishi, S.; Hiramatsu, K.; Araki, T.; Ueda, S.;
Tamamura, H.; Otaka, A.; Kusano, S.; Terakubo, S.; Nakashima, H.;
Broach, J. A.; Trent, J. O.; Wang, Z. X.; Peiper, S. C. MolecularꢀSize
(25) Tamamura, H.; Esaka, A.; Ogawa, T.; Araki, T.; Ueda, S.;
Wang, Z.; Trent, J. O.; Tsutsumi, H.; Masuno, H.; Nakashima, H.;
Yamamoto, N.; Peiper, S. C.; Otaka, A.; Fujii, N. StructureꢀActivity
Relationship Studies on CXCR4 Antagonists Having Cyclic
Pentapeptide Scaffolds. Org. Biomol. Chem. 2005, 3, 4392ꢀ4394.
(26) Våbenø, J.; Nikiforovich, G. V.; Marshall, G. R. A
Minimalistic 3D Pharmacophore Model for Cyclopentapeptide
CXCR4 Antagonists. Biopolymers (Pept. Sci.) 2006, 84, 459ꢀ471.
(27) Ueda, S.; Oishi, S.; Wang, Z. X.; Araki, T.; Tamamura, H.;
Cluzeau, J.; Ohno, H.; Kusano, S.; Nakashima, H.; Trent, J. O.;
Peiper, S. C.; Fujii, N. StructureꢀActivity Relationships of Cyclic
PeptideꢀBased Chemokine Receptor CXCR4 Antagonists: Disclosing
the Importance of SideꢀChain and Backbone Functionalities. J. Med.
Chem. 2007, 50, 192ꢀ198.
(28) Toniolo, C.; Bonora, G. M.; Bavoso, A.; Benedetti, E.; di
Blasio, B.; Pavone, V.; Pedone, C. Preferred Conformations of
Peptides Containing α,αꢀDisubstituted αꢀAmino Acids. Biopolymers
1983, 22, 205ꢀ215.
(29) Sun, N.; Avdeef, A. Biorelevant pKa (37 °C) Predicted from
the 2D Structure of the Molecule and Its pKa at 25 °C. J. Pharm.
Biomed. Anal. 2011, 56, 173ꢀ182.
Reduction of
a Potent CXCR4ꢀChemokine Antagonist Using
Orthogonal Combination of Conformationꢀ and SequenceꢀBased
Libraries. Angew. Chem. Int. Ed. Engl. 2003, 42, 3251ꢀ3253.
(12) Våbenø, J.; Nikiforovich, G. V.; Marshall, G. R. Insight into
the Binding Mode for Cyclopentapeptide Antagonists of the CXCR4
Receptor. Chem. Biol. Drug Des. 2006, 67, 346ꢀ354.
(13) Kawatkar, S. P.; Yan, M.; Gevariya, H.; Lim, M. Y.; Eisold,
S.; Zhu, X.; Huang, Z.; An, J. Computational Analysis of the
Structural Mechanism of Inhibition of Chemokine Receptor CXCR4
by Small Molecule Antagonists. Exp. Biol. Med. 2011, 236, 844ꢀ850.
(14) Demmer, O.; Dijkgraaf, I.; Schumacher, U.; Marinelli, L.;
Cosconati, S.; Gourni, E.; Wester, H. J.; Kessler, H. Design,
Synthesis, and Functionalization of Dimeric Peptides Targeting
Chemokine Receptor CXCR4. J. Med. Chem. 2011, 54, 7648ꢀ7662.
(30) Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid,
R. Novel Procedure for Modeling Ligand/Receptor Induced Fit
Effects. J. Med. Chem. 2006, 49, 534ꢀ553.
5
ACS Paragon Plus Environment