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References and notes
1. (a) Soto, C. Nat. Rev. Neurosci. 2003, 4, 49; (b) Chiti, F.; Dobson, C.
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3. Westermark, P.; Engstrom, U.; Johnson, K. H.; Westermark, G. T.;
Betsholtz, C. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 5036.
4. Elgersma, R. C.; Meijneke, T.; Posthuma, G.; Rijkers, D. T. S.;
Liskamp, R. M. J. Chem. Eur. J. 2006, 12, 3714.
Fig. 5. TEM-images of a racemic mixture of depsipeptide (2) and inverso-
depsipeptide (3). Scale bar represents 500 nm (conditions: 10 mg peptide/
mL 0.1% TFA/H2O, pH 1).
5. (a) Boettcher, C.; Schade, B.; Fuhrhop, J.-H. Langmuir 2001, 17, 873;
(b) Hirst, A. R.; Smith, D. K.; Feiters, M. C.; Geurts, H. P. M. Chem.
Eur. J. 2004, 10, 5901; (c) Mishra, B. K.; Garrett, C. C.; Thomas, B.
N. J. Am. Chem. Soc. 2005, 127, 4245; (d) Messmore, B. W.;
Sukerkar, P. A.; Stupp, S. I. J. Am. Chem. Soc. 2005, 127, 7992; (e)
Koga, T.; Matsuoka, M.; Higashi, N. J. Am. Chem. Soc. 2005, 127,
(Fig. 2). However, TEM images did not show the presence
of helical entities, rather flat ribbons were observed
(Fig. 5), which might be indicative of ‘racemate’ ribbons
through cross-recognition of depsipeptide 2 and inverso-
depispeptide 3 during the process of self-assembly.
´
´
17596; (f) Sly, J.; Kasak, P.; Gomar-Nadal, E.; Rovira, C.; Gorriz, L.;
Thordarson, P.; Amabilino, D. B.; Rowan, A. E.; Nolte, R. J. M.
Chem. Commun. 2005, 1255; (g) Becerril, J.; Escuder, B.; Miravet, J.
F.; Gavara, R.; Luis, S. V. Eur. J. Org. Chem. 2005, 481; (h) Pratim
Bose, P.; Drew, M. G. B.; Das, A. K.; Banerjee, A. Chem. Commun.
2006, 3196; (i) Brizard, A.; Kiagus Ahmad, R.; Oda, R. Chem.
Commun. 2007, 2275.
It is known from the literature that cross-recognition
between L- and D-peptides—to inhibit b-sheet- or amyloid
formation—is not often observed,15 probably due to a less
efficient hydrogen bonding network between both enantio-
mers.5e However, the racemic mixture of 2 and 3 did not
lead to self-sorting into individual left-handed (L-depsipep-
tide, 2) and right-handed (D-depsipeptide = inverso-depsi-
peptide, 3) nanostructures as was observed by Stupp and
co-workers in the case of their chiral dendron rodcoils.5d
Apparently, our backbone-modified depsipeptides, showed
a certain degree of cross-recognition between both enanti-
omers leading to the formation of supramolecular tapes,
possibly because the intermolecular interactions are domi-
nated by hydrophobic interactions of the amino acid side
chains rather than intermolecular hydrogen bonding. We
believe that insight into the driving forces of these recogni-
tion processes will be valuable for the design of supramo-
lecular bionanomaterials16 and for the development of
potential amyloid formation inhibitors.
6. Aggeli, A.; Nyrkova, I. A.; Bell, M.; Harding, R.; Carrick, L.;
McLeish, T. C. B.; Semenov, A. N.; Boden, N. Proc. Natl. Acad. Sci.
U.S.A. 2001, 98, 11857.
7. (a) Marini, D. M.; Hwang, W.; Lauffenburger, D. A.; Zhang, S.;
Kamm, R. D. Nano Lett. 2002, 4, 295; (b) Hwang, W.; Marini, D. M.;
Kamm, R. D.; Zhang, S. J. Chem. Phys. 2003, 118, 389; (c) Fishwick,
C. W. G.; Beevers, A. J.; Carrick, L. M.; Whitehouse, C. D.; Aggeli,
A.; Boden, N. Nano Lett. 2003, 3, 1475.
8. In case of peptides, see: (a) Shamovsky, I. L.; Ross, G. M.; Riopelle,
R. J. J. Phys. Chem. B 2000, 104, 11296. In general with amphiphilic
molecules, see: (b) Schnur, J. M.; Ratna, B. R.; Selinger, J. V.; Singh,
A.; Jyothi, G.; Easwaran, K. R. K. Science 1994, 264, 945; (c)
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9. Shin, I.; Lee, M.-R.; Lee, J.; Jung, M.; Lee, W.; Yoon, J. J. Org.
Chem. 2000, 65, 7667.
10. Synthesis of (2R,3R)-allyl-2-hydroxy-3-methylpentanoate (5): The
synthesis of (2R,3R)-2-hydroxy-3-methylpentanoic acid starting from
D-isoleucine was performed according to the procedures of Shin et al.9
Optical rotation and spectroscopic data were in agreement with the
literature. Crude (2R,3R)-2-hydroxy-3-methylpentanoic acid (1.81 g,
13.5 mmol) was dissolved in acetone (50 mL) and K2CO3 (2.85 g,
20.3 mmol) followed by the addition of allylbromide (2.4 mL,
27 mmol) and the obtained reaction mixture was stirred for 24 h.
After concentration in vacuo, the residue was redissolved in EtOAc
(50 mL) and the solution was washed with 5% aqueous NaHCO3
(2 ꢁ 25 mL) and brine (25 mL), dried (Na2SO4) and concentrated in
vacuo to obtain (2R,3R)-allyl-2-hydroxy-3-methylpentanoate (5) as a
colourless oil in 58% yield (1.34 g). Rf 0.76 (CH2Cl2/MeOH 98/2 v/v);
[a]D ꢀ5.8 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3): d 0.90 (t (J
7.4 Hz), 3H, dCH3), 0.99 (d (J 6.9 Hz), 3H, c0CH3), 1.32–1.39 (double
m, 2H, cCH2), 1.83 (m, 1H, bCH), 2.77 (br s, 1H, OH), 4.11 (d (J
3.9 Hz), 1H, aCH), 4.69 (m, 2H, ꢂO–CH2), 5.26–5.39 (m, 3H,
C@CH2), 5.93 (m, 1H, C@CH); 13C NMR (75 MHz, CDCl3): d 11.7,
15.4, 23.7, 39.1, 66.0, 74.8, 119.0, 131.5, 174.7.
11. Synthesis of Fmoc-D-Ala-D-Ilec-OH (6): The synthesis was carried out
as described for its enantiomer Fmoc-L-Ala-L-Ilec-OH.4 Based on
allyl ester 5 (930 mg, 5.4 mmol), compound 6 was obtained as a white
solid in 67% overall yield (403 mg). Rf 0.40 (CH2Cl2/MeOH 95/5 v/v);
[a]D +11.5 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3): d 0.93 (t (J 7.4
Hz), 3H, dCH3 Ilec), 1.01 (d (J 6.9 Hz), 3H, c0CH3 Ilec), 1.28–1.55
(5H, cCH2 Ilec) (2m)/bCH3 Ala (d (J 6.9 Hz)), 2.04 (m, 1H, bCH
Ilec), 4.23 (t (J 6.8 Hz), 1H, CH Fmoc), 4.39 (d (J 6.8 Hz), 2H, CH2
In conclusion, we described the synthesis of the enantio-
meric depsipeptide derived from the highly amyloidogenic
peptide sequence amylin(20–29) and reported on the ability
of these enantiomeric homochiral depsipeptides to direct
the handedness of the resulting supramolecular tapes.
Acknowledgements
These investigations were supported by the council for
Chemical Sciences of the Netherlands-Organization for
Scienctific Research (CW-NWO). Marc van Peski and
´
Rene Scriwanek (Center for Electron Microscopy, UMC
Utrecht) are acknowledged for their photographic artwork.
Supplementary data
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