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COSY: W. P Aue, E. Bartholdi, R. R. Ernst, J. Chem. Phys. 1976, 64, 2229; TOCSY: A. Bax, D. G. Davis, J. Magn. Reson. 1985, 65, 355; ROESY: A. A. Bothner-By, R. L. Stephens, J. Lee, C. D. Warren, R. W. Jeanloz, J. Am. Chem. Soc. 1984, 106, 811.
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COSY: W. P Aue, E. Bartholdi, R. R. Ernst, J. Chem. Phys. 1976, 64, 2229; TOCSY: A. Bax, D. G. Davis, J. Magn. Reson. 1985, 65, 355; ROESY: A. A. Bothner-By, R. L. Stephens, J. Lee, C. D. Warren, R. W. Jeanloz, J. Am. Chem. Soc. 1984, 106, 811.
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0031576336
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Ambiguous NOEs were assigned by using the program DYANA (P. Guntert, C. Mumenthaler, K. Wuthrich, J. Mol. Biol. 1997, 273, 283) in an iterative process. Each ambiguous NOE had one assignment that was consistent with all other nonsequential NOEs.
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5544242529
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Alternative helices were generated for an ACPC-Ala dodecamer using SYBYL (Tripos, St. Louis, MO) by imposing distance constraints for hydrogen bonds between appropriate C=O/H-N pairs. These structures were minimized using a continuum dielectric constant of 32.6, to simulate methanol, with the MMFF94s force field (T. A. Halgren, J. Comput. Chem. 1999, 20, 720.). Each of the resulting helical structures was taken to represent a possible local minimum in conformational energy for the dodecamer.
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0842299362
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note
-
It seemed possible that this design might bias each oligomer into either an 11- or 14/15-helical conformation based upon charge-charge interactions between side chains, allowing us to use rational principles to design α/β-oligomers with specific conformational preferences. A potential salt bridge between APC3 and Glu6 in 2 may preferentially stabilize an 11-helical conformation (helical wheel diagrams are included in the Supporting Information). In contrast, an interaction between APC3 and Lys6 in 3 may destabilize the 11-helical conformation, possibly favoring the 14/15-helical conformation. Complete evaluation of this hypothesis was not possible because of the severe resonance overlap observed for 2 and 3 in aqueous solution. In methanol, we do not expect the Glu side chain to be significantly deprotonated, minimizing the chance that salt-bridge formation would influence conformational preferences. Oligomers 2 and 3 show slightly different NOE patterns, suggesting that one helical conformation may be slightly more populated in one oligomer than in the other. Further investigations are under way to explore these possibilities.
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28
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0031576336
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10-helical domains in a synthetic α-peptide, see: V. Pavone, E. Benedetti, B. Di Blasio, C. Pedone, A. Santini, A. Bavoso, C. Toniolo, M. Crisma, L. Sartore, J. Biomol. Struct. Dyn. 1990, 7, 1321. It has been shown in one system that a three-center C=O⋯H⋯O=C interaction is higher in energy than an alternative two-center C= O⋯H hydrogen bond: J. Yang, S. H. Gellman, J. Am. Chem. Soc. 1998, 120, 9090.
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Guntert, P.1
Mumenthaler, C.2
Wuthrich, K.3
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0021192240
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10-helical domains in a synthetic α-peptide, see: V. Pavone, E. Benedetti, B. Di Blasio, C. Pedone, A. Santini, A. Bavoso, C. Toniolo, M. Crisma, L. Sartore, J. Biomol. Struct. Dyn. 1990, 7, 1321. It has been shown in one system that a three-center C=O⋯H⋯O=C interaction is higher in energy than an alternative two-center C= O⋯H hydrogen bond: J. Yang, S. H. Gellman, J. Am. Chem. Soc. 1998, 120, 9090.
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0025298602
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Sartore, L.9
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31
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0032500312
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