Interruption of a 310‐helix by Single Gly Residue In a Poly‐Aib Motif: A Crystallographic Study
by Jordi Sola
Solà, J.; Helliwell, M.; Clayden, J. Biopolymers. 2010, 95, 62-69
The structural influence of a single Gly residue inserted into an Aib16 homooligomer was studied in the solid state by... more The structural influence of a single Gly residue inserted into an Aib16 homooligomer was studied in the solid state by X-ray crystallography. The peptides N3Aib8GlyAib8PheNH2 (1) and CbzPheAib8GlyAib8 (2) were found to adopt well-defined helical structures, which are broadly 310 helical. Indeed, 2 is the longest crystallographic 310 helix thus far reported. However, in the region of the central Gly residue, a loosening of the 310 structure is observed in both peptides, with 1 clearly showing local adoption of an α-helical structure in the region of residues 7–9
N- versus C-Terminal Control over the Screw-Sense Preference of the Configurationally Achiral, Conformationally Helical Peptide Motif Aib8GlyAib8
by Jordi Sola
Solà, J.; Helliwell, M.; Clayden, J. J. Am. Chem. Soc. 2010, 132, 4548-4549
Conformational control over the screw sense of a helical 17-mer of achiral amino acids, Aib8GlyAib8, from a single... more Conformational control over the screw sense of a helical 17-mer of achiral amino acids, Aib8GlyAib8, from a single chiral residue located at the N-terminus is better than that from a single amino acid located at the C-terminus. X-ray crystallography indicates that Aib8GlyAib8 forms the longest 310 helical structure observed crystallographically to date.
Nanometer‐Range Communication of Stereochemical Information by Reversible Switching of Molecular Helicity
by Jordi Sola
Solà, J.; Fletcher, S.P.; Castellanos, A.; Clayden, J. Angew. Chem. Int. Ed. 2010, 49, 6836-6839
A long-distance call: The inversion of configuration at a stereogenic center led to a detectable switch in the... more A long-distance call: The inversion of configuration at a stereogenic center led to a detectable switch in the position of a 13C stereochemical probe 40 bonds (2.5 nm) away. Information was relayed between the sites by an inversion of screw sense in the intervening helix as illustrated (13C NMR signals were read as output).
Measuring screw-sense preference in a helical oligomer by comparison of 13C NMR signal separation at slow and fast exchange
by Jordi Sola
Jordi Solà, Gareth A. Morris and Jonathan Clayden. J. Am. Chem. Soc. 2011, 133, 3712
While an unequal population of rapidly interconverting left- and right-handed conformers of a helical oligomer can be... more While an unequal population of rapidly interconverting left- and right-handed conformers of a helical oligomer can be detected by circular dichroism, precise quantification of a conformer ratio has not previously been achieved. We demonstrate, using a set of labeled peptide analogues, that simple analysis of peak separation in their 13C NMR spectra at slow and fast exchange allows an accurate value for the ratio of helical conformers to be obtained. The method reports the ratio of conformers at the site of the label and can therefore be used to investigate local variations in helical conformational control.
Download (.pdf) Temperature-Dependent Loop Formation Kinetics In Flexible Peptides Studied by Time-Resolved Fluorescence Spectroscopy
Harekrushna Sahoo, Andreas Hennig and Werner M. Nau
International Journal of Photoenergy, 2006, doi:10.1155/IJP/2006/89638
Looping rates in short polypeptides can be determined by intramolecular fluorescence quenching of a... more Looping rates in short polypeptides can be determined by intramolecular fluorescence quenching of a 2,3-diazabicyclo[2.2.2]oct-2-ene-labeled asparagine (Dbo) by tryptophan. By this methodology, the looping rates in glycine-serine peptides with the structure Trp-(Gly-Ser)n-Dbo-NH2 of different lengths (n = 0–10) were determined in dependence on temperature in D2O and the activation parameters were derived. In general, the looping rate increases with decreasing peptide length, but the shortest peptide (n=0) shows exceptional behavior because its looping rate is slower than that for the next longer ones (n=1,2). The activation energies increase from 17.5 kJ mol−1 for the longest peptide (n=10) to 20.5 kJ mol−1 for the shortest one (n=0), while the pre-exponential factors (log(A/s−1)) range from 10.20 to 11.38. The data are interpreted in terms of an interplay between internal friction (stiffness of the biopolymer backbone and steric hindrance effects) and solvent friction (viscosity-limited diffusion). For the longest peptides, the activation energies resemble more and more the value expected for solvent viscous flow. Internal friction is most important for the shortest peptides, causing a negative curvature and a smaller than ideal slope (ca. –1.1) of the double-logarithmic plots of the looping rates versus the number of peptide chain segments (N). Interestingly, the corresponding plot for the pre-exponential factors (logA versus logN) shows the ideal slope (–1.5). While the looping rates can be used to assess the flexibility of peptides in a global way, it is suggested that the activation energies provide a measure of the “thermodynamic” flexibility of a peptide, while the pre-exponential factors reflect the “dynamic” flexibility.
Quantitative analysis of low-abundance peptides in HeLa cell cytoplasm by targeted liquid chromatography/mass spectrometry and stable isotope dilution: emphasising the distinction between peptide detection and peptide identification.
by Sarah Martin
Rapid Communications in Mass Spectrometry 24(7):1093-104
Thierry Le Bihan, Ramon Grima, Sarah Martin, Thorsten Forster, Yann Le Bihan
We present the application of a targeted liquid chromatography/mass spectrometry (LC/MS) approach developed on a... more We present the application of a targeted liquid chromatography/mass spectrometry (LC/MS) approach developed on a linear ion trap for the evaluation of the abundance of cytoplasmic proteins from a HeLa cell extract. Using a standard data-dependent approach, we identified some specific peptides from this extract which were also commercially available in their AQUA form (use for absolute quantitation). For some of the peptides, we observed a non-linear response between the intensity and the added quantity which was then fitted using a quadratic fit. All AQUA peptides spiked into a mix of 3 microg of the HeLa cell digest extract were detected down to 16 fmol. We placed an emphasis on peptide detection which, in this study, is performed using a combination of properties such as three specific Q3-like ion signatures (for a given Q1-like selection) and co-elution with the AQUA peptide counterparts. Detecting a peptide without necessarily identifying it using a search engine imposes less constraint in terms of tandem mass (MS/MS) spectra purity. An example is shown where a peptide is detected using those criteria but could not be identified by Mascot due to its lower abundance. To complement this observation, we used a cross-correlation analysis approach in order to separate two populations of MS/MS fragments based on differences in their elution patterns. Such an approach opens the door to new strategies to analyse lower intensity peptide fragments. An in silico analysis of the human trypsinosome allows the evaluation of how unique are the sets of features that we are using for peptide detection.
Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505)
N. Dietis, J. McDonald, S. Molinari, R. Guerrini, G. Calo, D. J. Rowbotham & D. G. Lambert
British Journal of Anaesthesia 108 (2): 262–70 (2012)
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