268729-12-0Relevant articles and documents
Stereodependent and solvent-specific formation of unusual β-structure through side chain-backbone H-bonding in C4(S)-(NH2/OH/NHCHO)-L-prolyl polypeptides
Bansode, Nitin D.,Madhanagopal,Sonar, Mahesh V.,Ganesh, Krishna N.
, (2017)
It is shown that C4(S)-NH2/OH/NHCHO-prolyl polypeptides exhibit PPII conformation in aqueous medium, but in a relatively hydrophobic solvent trifluoroethanol (TFE) transform into an unusual β-structure. The stereospecific directing effect of H-bonding in defining the specific structure is demonstrated by the absence of β-structure in the corresponding C4(S)-guanidinyl/(NH/O)-acetyl derivatives and retention of β-structure in C4(S)-(NHCHO)-prolyl polypeptides in TFE. The distinct conformations are identified by the characteristic CD patterns and supported by Raman spectroscopic data. The solvent dependent conformational effects are interpreted in terms of intraresidue H-bonding that promotes PPII conformation in water, switching over to interchain H-bonding in TFE. The present observations add a new design principle to the growing repertoire of strategies for engineering peptide secondary structural motifs for innovative nanoassemblies and new biomaterials.
Conformational changes associated with post-translational modifications of pro143 in Skp1 of dictyostelium -a dipeptide model system
Karunaratne, Chamini V.,Weldeghiorghis, Thomas K.,West, Christopher M.,Taylor, Carol M.
supporting information, p. 15170 - 15175 (2015/02/19)
Prolyl hydroxylation and subsequent glycosylation of the E3SCF ubiquitin ligase subunit Skp1 affects its conformation and its interaction with F-box proteins and, ultimately, O2-sensing in the organism. Taking a reductionist approach to understand the molecular basis for these effects, a series of end-capped Thr-Pro dipeptides was synthesized, tracking the sequential post-translational modifications that occur in the protein. The conformation of the pyrrolidine ring in each compound was gauged via coupling constants (3JHα,Hβ) and the electronegativity of the Cγ-substituents by chemical shifts (13C). The equilibrium between the cis-trans conformations about the central prolyl peptide bond was investigated by integration of signals corresponding to the two species in the 1H NMR spectra over a range of temperatures. These studies revealed an increasing preference for the trans-conformation in the order Pro a reduced rate for the trans-to-cis conversion and a significant increase in the cis-to-trans conversion upon hydroxylation of the proline residue in the dipeptide. NOE experiments suggest that the Thr side chain pushes the sugar away from the pyrrolidine ring. These effects, which depended on the presence of the N-terminal Thr residue, offer a mechanism to explain altered properties of the corresponding full-length proteins.