Organic Letters
Letter
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strongly lipophilic solvent 1-octanol already at temperatures
above 30 °C. This effect has already been reported for
the hypothesis of parallel helical coiled coils, the CD spectra in a
1:1 100 mM mixture of TFE in SDS were recorded for all
Information). TFE is known to enhance intramolecular α-
helicity but to decrease intermolecular interactions.22
A
destruction of the homocoiled−coil binding motif results in a
significant decrease in the θ222/θ208 ratio from SDS to 50%
TFE in SDS.19 For all compounds, the R decrease, confirmed the
supramolecular organization of peptides in aqueous sodium
dodecyl sulfate.
All of the synthesized analogues were tested in an agar bacterial
growth assays at a dose of 20 μg/disk on Gram-positive Bascillus
subtilis, and only the native alamethicin was found active.
Therefore, we could suspect that due to steric hindrance the
hexameric self-association of alamethicin needed to form the
pore supramolecular structure is prevented.23
In conclusion, this study reports an easy access to α,α-
disubstituted disilylated amino acids. These original amino acid
derivatives are directly usable in SPPS and permit to conserve the
helicoidal secondary structure of the peptide in which they are
inserted. This amino acid surrogate of the Aib offers the
possibility to strengthen the hydrophobicity of the peptide, and
one can expect they would certainly reinforce their ability to cross
membranes.
(7) Cavelier, F.; Marchand, D.; Martinez, J. Chem. Biodiversity 2008, 5,
1279.
(8) Fanelli, R.; Jeanne-Julien, L.; Rene,
Amino Acids 2015, 47, 1107.
́
A.; Martinez, J.; Cavelier, F.
(9) Brunel, J. M. Protein Pept. Lett. 2005, 12, 281.
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2005, 24, 1780. (c) Merget, M.; Gunther, K.; Bernd, M.; Gunther, E.;
̈
̈
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
Tacke, R. J. Organomet. Chem. 2001, 628, 183. (d) Vivet, B.; Cavelier, F.;
Martinez, J. Eur. J. Org. Chem. 2000, 2000, 807. (e) Martin, C.;
Vanthuyne, N.; Miramon, H.; Martinez, J.; Cavelier, F. Amino Acids
2012, 43, 649.
(11) Marchand, D.; Martinez, J.; Cavelier, F. Eur. J. Org. Chem. 2008,
2008, 3107.
■
S
Experimental procedures and characterization data (PDF)
(12) (a) Min, G. K.; Skrydstrup, T. J. Org. Chem. 2012, 77, 5894.
́
(b) Skoda-Foldes, R.; Kollar, L.; Heil, B. J. Organomet. Chem. 1991, 408,
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297.
(13) Eaborn, C.; Pant, B. C.; Peeling, E. R. A.; Taylor, S. C. J. Chem. Soc.
C 1969, 2823.
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Pavone, V.; Pedone, C. Biopolymers 1985, 24, 1759. (b) Peggion, C.;
Moretto, A.; Formaggio, F.; Crisma, M.; Toniolo, C. Biopolymers 2013,
100, 621.
AUTHOR INFORMATION
Corresponding Authors
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Notes
(15) Karle, I. L.; Kaul, R.; Rao, R. B.; Raghothama, S.; Balaram, P. J. Am.
Chem. Soc. 1997, 119, 12048.
The authors declare no competing financial interest.
(16) (a) Yang, P.; Wu, F.-G.; Chen, Z. J. Phys. Chem. C 2013, 117, 3358.
(b) Peggion, C.; Jost, M.; De Borggraeve, W. M.; Crisma, M.;
Formaggio, F.; Toniolo, C. Chem. Biodiversity 2007, 4, 1256. (c) Futaki,
S.; Asami, K. Chem. Biodiversity 2007, 4, 1313. (d) Fox, R. O.; Richards,
F. M. Nature 1982, 300, 325.
(17) Ben Haj Salah, K.; Inguimbert, N. Org. Lett. 2014, 16, 1783.
́
(18) Valko, K.; Bevan, C.; Reynolds, D. Anal. Chem. 1997, 69, 2022.
(19) De Zotti, M.; Ballano, G.; Jost, M.; Salnikov, E. S.; Bechinger, B.;
ACKNOWLEDGMENTS
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N.I. acknowledges the “Comite
́
des Pyren
́
ee
́
s Orientales de la
Ligue Nationale Contre le Cancer and the BQR de l’Universite
de Perpignan Via Domitia“ for financial support. Dalila Argentin
(University of Milan) is gratefully acknowledged. The
Plateforme de mesures de diffraction X of the “Universite
Lorraine” is thanked for crystallographic facilities.
́
́
de
Oancea, S.; Crisma, M.; Toniolo, C.; Formaggio, F. Chem. Biodiversity
2014, 11, 1163.
(20) Zhou, N. E.; Zhu, B.-Y.; Kay, C. M.; Hodges, R. S. Biopolymers
1992, 32, 419.
(21) Jung, G.; Dubischar, N.; Leibfritz, D. Eur. J. Biochem. 1975, 54,
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