Laureates: awards and Honors, sCs FaLL Meeting 2010ꢀ
CHIMIAꢀ2011,ꢀ65,ꢀNo.ꢀ4ꢀ 267
Lipman, P. J. Steinbach, M. Kumke, W. A.
Eaton, Proc. Natl. Acad. Sci. USA 2005, 102,
2754; b) a) M. Cordes, A. Kottgen, C. Jasper,
O. Jacques, H. Boudebous, B. Giese, Angew.
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destabilize the PPII helix whereas capped application. We are currently investigating
(uncharged) termini favor the PPII helix the utility of appropriately functionalized
relative to the PPI helix.[15] The effect of oligoprolines as cell-penetrating peptides,
functional groups in the γ-position of pro- for tumor targeting, and for the develop-
line residues depends also on the absolute ment of semiconducting materials. In addi-
configuration at this chiral center. (4R)- tion, the versatility of Azp residues is used
Configured proline derivatives with elec- for the development of functionalizable
tron-withdrawing groups such as azides collagen model peptides.[19]
[6] M. Rothe, H. Rott, J. Mazanek, J. Pept., Proc.
Eur. Pept. Symp., 14th 1976, 309.
[7] F. Rabanal, M. D. Ludevid, M. Pons, E. Giralt,
Biopolymers 1993, 33, 1019.
[8] A. Rath, A. R. Davidson, C. M. Deber,
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[9] S. Kakinoki, Y. Hirano, M. Oka, Polymer Bull.
2005, 53, 109.
[10] G. Fischer, Chem. Soc. Rev. 2000, 29, 119.
[11] M. Kümin, L.-S. Sonntag, H. Wennemers, J.
Am. Chem. Soc. 2007, 129, 566.
at C(4) stabilize the PPII helix relative to
the PPI helix.[11] Likewise (4S)-configured
Received: February 28, 2011
proline derivatives with hydrogen-bond
[1] For examples see: a) J. Iriondo-Alberdi, K.
donating groups such as ammonium ions
Laxmi-Reddy, B. Bouguerne, C. Staedel, I. Huc,
ChemBioChem 2010, 11, 1679; b) I. Geisler, J.
at C(4) also stabilize the PPII helix relative
to the PPI helix.[13] These stabilizing and
destabilizing effects correlate well with the
influence of the substituent and the abso-
lute configuration at C(4) on the cis:trans
amide conformer equilibrium.[13,14] They
can be easily monitored and analyzed in
simpler model compounds such as the
respective acetylated methyl esters of the
type Ac-Xaa-OCH3.[11,13,14]
Chmielewski, Chem. Biol. Drug Des. 2009, 73,
39; c) B. A. Smith, D. S. Daniels, A. E. Coplin,
G. E. Jordan, L. M. McGregor, A. Schepartz, J.
Am. Chem. Soc. 2008, 130, 2948; d) S. Pujals,
E. Giralt, Adv. Drug Del. Rev. 2008, 60, 473;
e) J. Farrera-Sinfreu, E. Giralt, S. Castel, F.
Albericio, M. Royo, J. Am. Chem. Soc. 2005,
127, 9459.
[12] R. S. Erdmann, M. Kümin, H. Wennemers,
Chimia 2009, 63, 197.
[13] M. Kuemin, Y. A. Nagel, S. Schweizer, F.
W. Monnard, C. Ochsenfeld, H. Wennemers,
Angew. Chem. Int. Ed. 2010, 49, 6324.
[14] L.-S. Sonntag, S. Schweizer, C. Ochsenfeld,
H. Wennemers, J. Am. Chem. Soc. 2006, 128,
14697.
[15] M. Kuemin, S. Schweizer, C. Ochsenfeld, H.
Wennemers, J. Am. Chem. Soc. 2009, 131,
15474.
[2] For examples see: a) M. A. Schmitt, B.
Weisblum, S. H. Gellman, J. Am. Chem. Soc.
2004, 126, 6848; b) D. Liu, W. F. DeGrado, J.
Am. Chem. Soc. 2001, 123, 7553.
[3] For examples see: a) K. M. Bonger, V. V.
Kapoerchan, G. M. Grotenbreg, C. J. v.
Koppen, C. M. Timmers, G. A. v. d. Marel, H. S.
Overkleeft, Org. Biomol. Chem. 2010, 8, 1881;
b) S.-G. Lee, S. Hershberger, J. Chmielewski,
Curr. Top. Med. Chem. 2007, 7, 928; c) O. M.
Stephens, S. Kim, B. D. Welch, M. E. Hodson,
M. S. Kay, A. Schepartz, J. Am. Chem. Soc.
2001, 123, 7553.
[4] For examples see: a) L. E. Russel, J. A. Fallas,
J. D. Hartgerink, J. Am. Chem. Soc. 2010,
132, 3242; b) M. M. Pires, D. E. Przybyla, J.
Chmielewski, Angew. Chem. Int. Ed. 2009,
48, 7813; c) F. W. Kotch, R. T. Raines, Proc.
Natl. Acad. Sci. USA 2006, 103, 3028; d) U.
Kusebauch, S. A. Cadamuro, H.-J. Musiol, M.
O. Lenz, J. Wachtveitl, L. Moroder, C. Renner,
Angew. Chem. Int. Ed. 2006, 45, 7015.
[16] M. Kuemin, J. Engel, H. Wennemers, J. Pept.
Sci. 2010, 16, 596.
[17] a) V. V. Rostovtsev, L. G. Green, L. G.; V. V.
Fokin, K. B. Sharpless, Angew. Chem. Int. Ed.
2002, 41, 2596; b) C. W. Tornøe, C. Christensen,
M. Meldal, M. J. Org. Chem. 2002, 67, 3057.
[18] J. M. Holub, H. Jang, K. Kirshenbaum, Org.
Biomol. Chem. 2006, 4, 1497.
5. Conclusions
Azidoproline-containing oligoprolines
are attractive molecular scaffolds since
they allow not only facile functionaliza-
tion but adopt conformationally well-
defined helical conformations already at
short chain lengths (≥6 residues). These
features render Azp-containing oligo-
prolines intriguing for manifold different
applications. Our basic conformational
studies demonstrated that the functional
groups at the N- and C-termini as well as
the absolute configuration of C(4) have
to be selected carefully depending on the
[19] R. S. Erdmann, H. Wennemers, J. Am. Chem.
Soc. 2010, 132, 13957.
[5] For examples of the use of oligoprolines as
‘molecular rulers’, see a) B. Schuler, E. A.