Biotin tethered homotryptamine derivatives: High affinity probes of the human serotonin transporter (hSERT)

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 6, 2011, Pages 1678-1682

  Tomlinson, Ian D ^a   Iwamoto, Hideki ^b   Blakely, Randy D ^b,c   Rosenthal, Sandra J ^a,b  

^a VANDERBILT UNIVERSITY   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c 1807 Station B ^*  (United States)

Author keywords

Homotryptamine; Leak current; Quantum dot; Serotonin; SERT antagonist

Indexed keywords

BIOTIN; CYCLOHEXYLAMINE; HOMOTRYPTAMINE DERIVATIVE; PYRIDINE DERIVATIVE; QUANTUM DOT; SEROTONIN TRANSPORTER; STREPTAVIDIN; TETRAHYDROPYRIDINE; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CELL MEMBRANE POTENTIAL; CONTROLLED STUDY; LIGAND BINDING; MOLECULAR PROBE; NONHUMAN; OOCYTE; PROTEIN BINDING; XENOPUS LAEVIS;

AFFINITY LABELS; ANIMALS; BIOTIN; HUMANS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TRYPTAMINES; XENOPUS;

EID: 79952364017     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.01.102     Document Type: Article

References (17)

1. Y. Qian, H.E. Melikian, D.B. Rye, A.I. Levey, and R.D. Blakely J. Neurosci. 15 1995 1261
2. L.D. Jayanthi, D.J. Samuvel, and S. Ramamoorthy J. Biol. Chem. 279 2004 19315
3. J. McBride, J. Treadway, L.C. Feldman, S.J. Pennycook, and S.J. Rosenthal Nano Lett. 6 2006 1496
4. S.J. Rosenthal, J. McBride, S.J. Pennycook, and L.C. Feldman Surf. Sci. Rep. 62 2007 111
5. M. Bruchez Jr., M. Moronne, P. Gin, S. Weiss, and A.P. Alivisatos Science 281 1998 2013
6. W.C.W. Chan, and S. Nie Science 281 1998 2016
7. S.J. Rosenthal, I.D. Tomlinson, S. Schroter, E. Adkins, L. Swafford, Y. Wang, L.J. DeFelice, and R.D. Blakely J. Am. Chem. Soc. 124 2002 4586
8. I.D. Tomlinson, J.N. Mason, R.D. Blakely, and S.J. Rosenthal Bioorg. Med. Chem. Lett. 15 2005 5307
9. I.D. Tomlinson, M.R. Warnerment, J.N. Mason, M.J. Vergne, D.M. Hercules, R.D. Blakely, and S.J. Rosenthal Bioorg. Med. Chem. Lett. 17 2007 5656
10. E.L. Bentzen, I.D. Tomlinson, J.N. Mason, P. Gresch, D. Wright, E. Sanders-Busch, R. Blakely, and S.J. Rosenthal Bioconjugate Chem. 16 2005 1488
11. J. Guillaume, C. Dumont, J. Laurent, and I. Ne′de′lec Eur. J. Med. Chem. 22 1987 33
12. IDT357 (8) was synthesized by dissolving Biotin-PEG5000-NHS (0.2 g) in methylene chloride (100 ml) and 11-(4-(1H-indol-3-yl)-5,6-dihydrpyridin-1(2H)- yl)undecylamine (17a) 0.015 g was added. This solution was stirred for 18 h then evaporated under reduced pressure. The product was repeatedly washed with diethylether (5 × 100 ml) to yield 0.14 g of (8) as a pale yellow solid. Compounds (9)-(11) were synthesized using the same protocol.
13. 3) δ 136.78, 131.08, 125.22, 122.00, 121.14, 120.72, 119.86, 119.65, 118.47, 111.27, 54.70, 33.63, 32.57, 28.99, 27.53
14. 6) δ 167.95, 136.89, 134.44, 134.40, 131.56, 126.00, 124.54, 123.10, 122.99, 119.98, 119.33, 116.80, 115.53, 111.81, 45.61, 37.35, 29.36, 28.80, 28.50, 27.84, 26.20, 26.08, 23.70
15. IDT374 (13) was synthesized by dissolving Biotin-PEG5000-NHS (0.2 g) in dry dimethyl formamide (10 ml) and 2-(11-((4-(1H-indol-3-yl)cyclohex-3-enyl) (methyl)aminoundecyl)isoindoline-1,3-dione (0.016 g) was added. The solution was stirred for 18 h then tenta gel derivatized with NHS was added (1 g) and stirred for 6 h the solution was filtered and evaporated and the resulting material was dissolved in deionised water then filtered and evaporated to yield IDT374 (0.16 g) as a pale brown solid.
16. Compound (14). Using the same synthetic protocol as was used to synthesize (8); 120 mg of IDT364 (12) was obtained from 150 mg of Biotin-PEG5000-NHS and methylamine (33%, 5 ml) dissolved in methanol.
17. J.A. Deskus, J.R. Epperson, C.P. Sloan, J.A. Cipollina, P. Dextraze, J. Qian-Cutrone, Q. Gao, B. Ma, B.R. Beno, G.K. Mattson, T.F. Molski, R.G. Krause, M.T. Taber, N.J. Lodge, and R.J. Mattson Bioorg. Med. Chem. Lett. 17 2007 3099