Linked Life Data

18662036

Source:http://linkedlifedata.com/resource/pubmed/id/18662036

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2008-9-1
pubmed:abstractText
The conformational properties of foldamers generated from alphagamma 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 conformational space. This model sequence was anticipated to be a short segment of the alphagamma C12 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 C12 hydrogen bonds were obtained at the N-terminus, while a novel C17 hydrogen-bonded gamma alpha gamma turn was observed at the C-terminus. In the other two polymorphs, isolated C9 and C7 hydrogen-bonded turns were observed at Gpn (2) and Gpn (4). Isolated C12 and C9 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 C12 helix conformation. Lengthening of the (alphagamma) 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 alphagamma C12 helix. These results establish that conformational fragility is manifested in short hybrid alphagamma sequences despite the choice of conformationally constrained residues, while stable helices are formed on chain extension.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-6904
pubmed:author
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6595-606
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Multiple conformational states in crystals and in solution in alphagamma hybrid peptides. Fragility of the C12 helix in short sequences.
pubmed:affiliation
Molecular Biophysics Unit, Indian Institute of Science, Bangalore-560012, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't