Linked Life Data

16392797

Source:http://linkedlifedata.com/resource/pubmed/id/16392797

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-5
pubmed:abstractText
Four residues making almost a complete 180 degrees turn in the direction of the peptide chain define a reverse turn, a common motif and recognition site in proteins. Cyclization between residues i and i + 3 and incorporation of heterochiral dipeptides (such as d-Pro-l-Pro) in the i + 1 and i + 2 positions are used to constrain a peptide to a reverse-turn conformation. A combined approach, cyclic tetrapeptides (CTPs) based on heterochiral dipeptides of chimeric amino acids, is evaluated as minimalist scaffolds for reverse-turn conformations. Cyclo-(d-Pro-l-Pro-d-Pro-l-Pro) has been studied with density functional theory (DFT) calculations and molecular dynamics simulations. The all-trans amide conformer was the most stable in vacuo, while the cis-trans-cis-trans (ctct) or trans-cis-trans-cis (tctc) amide conformer was more favored in water due to its large dipole moment. Different conformations could be selectively stabilized by different substitutions on the proline rings. Due to the small 12-membered ring and exocyclic constraints, conformational interconversions could only occur at high temperature. The presence of seven hydrogens on each ring that could be functionalized offers an overwhelming diversity to design molecules to probe receptors. The spatial relationships of C(alpha)-C(beta) vectors of reverse turns in proteins were subjected to principal component analysis for determination of the relative orientation of the C(alpha)-C(beta) vectors. Most reverse-turn structures could be mimicked effectively with a subset of CTP scaffolds with an root-mean-square displacement (RMSD) of approximately 0.5 A. Structural diversity of CTP scaffolds could be enhanced by the incorporation of proline analogues, such as azaproline (azPro) or pipecolic (Pip), azapipecolic (azPip), nipecotic (Nip), and isonipecotic (Inp) acids.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-24
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Engineering cyclic tetrapeptides containing chimeric amino acids as preferred reverse-turn scaffolds.
pubmed:affiliation
Center for Computational Biology and Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural