Multiple conformational states in crystals and in solution in alpha gamma hybrid peptides. Fragility of the C-12 helix in short sequences
Data(s) |
05/09/2008
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Resumo |
The conformational properties of foldamers generated from alpha gamma hybrid peptide sequences have been probed in the model sequence Boc-Aib-Gpn-Aib-Gpn-NHMe. The choice of alpha-aminoisobutyryl (Aib) and gabapentin (Gpn) residues greatly restricts sterically accessible coil formational space. This model sequence was anticipated to be a short segment of the alpha gamma C-12 helix, stabilized by three successive 4 -> 1 hydrogen bonds, corresponding to a backbone-expanded analogue of the alpha polypeptide 3(10)-helix. Unexpectedly, three distinct crystalline polymorphs were characterized in the solid state by X-ray diffraction. In one form, two successive C-12 hydrogen bonds were obtained at the N-terminus, while a novel C-17 hydrogen-bonded gamma alpha gamma turn was observed at the C-terminus. In the other two polymorphs, isolated C-9 and C-7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C-12 and C-9 turns were also crystallographically established in the peptides Boc-Aib-Gpn-Aib-OMe and Boc-Gpn-Aib-NHMe, respectively. Selective line broadening of NH resonances and the observation of medium range NH(i)<-> NH(i+2) NOEs established the presence of conformational heterogeneity for the tetrapeptide in CDCl3 solution. The NMR results are consistent with the limited population of the continuous C-12 helix conformation. Lengthening of the (alpha gamma)(n) sequences in the nonapeptides Boc-Aib-Gpn-Aib-Gpn-Aib-Gpn-Aib-Gpn-Xxx (Xxx = Aib, Leu) resulted in the observation of all of the sequential NOEs characteristic of an alpha gamma C-12 helix. These results establish that conformational fragility is manifested in short hybrid alpha gamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension. |
Formato |
application/pdf |
Identificador |
http://eprints.iisc.ernet.in/27408/1/414.pdf Chatterjee, S and Vasudev, PG and Ananda, K and Ananda, Kuppanna and Raghothama, Srinivasarao and Shamala, N and Balaram, Padmanabhan (2008) Multiple conformational states in crystals and in solution in alpha gamma hybrid peptides. Fragility of the C-12 helix in short sequences. In: Journal of Organic Chemistry, 73 (17). pp. 6595-6606. |
Publicador |
American Chemical Society |
Relação |
http://pubs.acs.org/doi/abs/10.1021/jo8009819 http://eprints.iisc.ernet.in/27408/ |
Palavras-Chave | #Molecular Biophysics Unit |
Tipo |
Journal Article PeerReviewed |