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differ from that of voltage-dependent channels, for
References and Notes
which there is an increasing body of structural infor-
mation.17 This raises the possibility that NPPB may
inhibit a wide range of different K+ channels, irrespec-
tive of overall structure, and its interaction with the
channels may be based on highly conserved regions such
as the K-channel signature sequence responsible for
channel selectivity.1 It should, however, be noted that
the effect of NPPB on the large conductance K+ chan-
nel in this study differs from the previously reported
effect of increasing current in oocytes expressing cloned
human BK channel,11 which may indicate that their
structural similarity may not be that high.
1. Hille, B. Ion Channels of Excitable Membranes, 3rd ed.;
Sinauer: Sunderland, 2001; p 814.
2. Greger, R. Methods Enzymol. 1990, 191, 793.
3. Wangemann, P.; Wittner, M.; Di Stefano, A.; Englert,
H. C.; Lang, H. J.; Schlatter, E.; Grefer, R. Pfluegers Arch.
1986, 407, S128.
4. Zimmerman, S.; Frachisse, J. M.; Thomine, S.; Barbier-
Brygoo, H.; Guern, J. Plant Physiol. Biochem. 1998, 36, 665.
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1996, 93, 8134.
6. Trebacz, K.; Simonis, W.; Schonknecht, G. Plant Cell
Physiol. 1997, 38, 550.
7. Garrill, A.; Tyerman, S. D.; Findlay, G. P.; Ryan, P. R.
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8. Thomine, S.; Guern, J.; Barbier-Brygoo, H. J. Membr. Biol.
1997, 159, 71.
9. Luhring, H. Protoplasma 1986, 133, 19.
Further investigation of the interaction of NPBB with
K+ channels is possible through the use of inhibitors
with closely related structures. One such compound,
NPBB, differs from NPPB by a simple methylene
extension. Similar extensions in Na+ channel inhibitors
(for example the difference between phenamil and ben-
zamil) increase the efficacy of the inhibitor.18 We found
no significant difference in the effect of NPPB and
NPBB on channel amplitude; thus, the methylene
extension does not appear to evoke greater efficacy
toward the large conductance K+ channel. Clearly, this
is an area in which further studies are warranted and
our synthetic technique should enable to production of
a range of potentially interesting compounds.
10. Laver, D. R.; Walker, N. A. J. Membrane Biol. 1991, 120,
131.
11. Gribhoff, V. K.; LumRagan, J. T.; Boissard, C. G.; Post-
Munson, D. J.; Meanwell, N. A.; Starrett, J. E.; Kozlowski,
E. S.; Romine, J. L.; Trojnacki, J. T.; McKay, M. C.; Zhong,
J.; Dworetzky, S. I. Mol. Pharmacol. 1996, 50, 206.
12. Branchini, B. R.; Murtiashaw, M. H.; Egan, L. A. Bio-
chem. Biophys. Res. Commun. 1991, 176, 459.
13. Gregor, R.; Englert, H.; Lang, H. J.; Hropot, M. Ger.
Offen, DE 85-3527409 19850731, 1987.
14. This aldehyde was prepared by oxidizing 4-phenyl-1-
butanol with PDC. The oxidation was incomplete and the thus
obtained 2:1 mixture of 4-phenyl-1-butryaldehyde and
4-phenyl-1-butanol was used after distillation.
15. Hamill, O. P.; Marty, A.; Neher, E.; Sakmann, B.; Sig-
worth, F. J. Pflugers Arch. 1981, 391, 85.
In summary, we present a simple method for the pre-
paration of NPPB and NPBB which should be amen-
able to a range of related compounds where a range of
the required aldehydes and arylamines is available. We
also show that these two inhibitors can reduce channel
amplitude of the large conductance K+ channel present
in cytoplasmic droplets of the alga N. hookeri.
16. Garrill, A. Biochem. Mol. Biol. Edu. 2001, 28, 318.
17. Schachtman, D. P. Biochim. Biophys. Acta 2000, 1465, 127.
18. Li, J. H.-Y.; Cragoe, E. J., Jr.; Lindemann, B. J. Membr.
Biol. 1987, 95, 171.