Like shock absorbers in cars
short helical peptides rich in C
α
‐tetrasubstituted amino acids change their elongation responding to an external stimulus. In fact, they behave like molecular springs ...and adjust their conformation according to the polarity of the medium in which they are dissolved. In solvents of high polarity (like water) they shrink, adopting an α‐helix conformation, while in solvents of low polarity (like isopropanol) they elongate, adopting a 3
10
‐helix conformation. Details of this behavior are to be found in the Full Paper by P. Scrimin, S. Mammi, L. Randaccio, L. Pasquato et al. on page 407 ff.
The two peptides, rich in Cα‐tetrasubstituted amino acids, Ac‐Aib‐L‐(αMe)Val‐Aib2‐L‐His‐NH2 (1) and Ac‐Aib‐L‐(αMe)Val‐Aib2‐O‐tBu (2 a) are prevalently helical. They present the unique property of ...changing their conformation from the α‐ to the 310‐helix as a function of the polarity of the solvent: α in more polar solvents, 310 in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two‐dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X‐ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 310‐helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 310‐helix and the use of the CD technique for its assessment.
Peptides that behave like a solvent‐sensitive molecular spring: Two short peptides elongate, adopting a 310‐helix conformation, in solvents of low polarity, while they shrink, adopting an α‐helix conformation, in highly polar solvents (see illustration).
The two peptides, rich in C(alpha)-tetrasubstituted amino acids, Ac-Aib-L-(alphaMe)Val-Aib(2)-L-His-NH(2) (1) and Ac-Aib-L-(alphaMe)Val-Aib(2)-O-tBu (2 a) are prevalently helical. They present the ...unique property of changing their conformation from the alpha- to the 3(10)-helix as a function of the polarity of the solvent: alpha in more polar solvents, 3(10) in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two-dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X-ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 3(10)-helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 3(10)-helix and the use of the CD technique for its assessment.
The long and the short of it: Just by changing the polarity of the solvent the highly folded heptapeptide Ac‐Aib‐L‐(αMe)Val‐Aib2‐L‐His‐NH2 converts from an α into a 310 helix (see picture). The ...equilibrium constant between the two conformations correlates with the empirical solvent polarity parameter E${{{\rm {\rm N}}\atop {\rm {\rm T}}}$. Molecular dynamics calculations show that the peptide elongates (310 helix) or shortens (α helix) on switching from one conformation to the other.
Nanozyme mit einem Herz aus Gold: Durch das Aufpfropfen eines Dodecapeptids auf die Oberfläche von Goldnanopartikeln (siehe Bild) ließ sich ein funktionelles künstliches Protein herstellen. Dieses ...System katalysiert die Hydrolyse von Carbonsäureestern und zeigt enzymartige Eigenschaften.
Hydrogen‐Bonded Helical Organic Nanotubes Pantoş, G. Dan; Pengo, Paolo; Sanders, Jeremy K. M.
Angewandte Chemie,
March 19, 2007, Volume:
119, Issue:
13
Journal Article
Verdrillte Röhren: Die Selbstorganisation kleiner organischer Moleküle ist ein neuer Syntheseansatz für Nanoröhren mit helicaler Chiralität. Aminosäurederivate von Naphthalindiimid bilden in Lösung ...wie im festen Zustand solche Assoziate. Die Chiralität der Nanoröhren wird durch die Aminosäure festgelegt, hängt aber nicht von der Art der Seitenketten ab.
Triethylene glycol-functionalized gold nanoparticles have been obtained by exchange reaction from dodecanthiolate-MPCs.
1H NMR allowed to determine a 1:1 ratio of alkyl- to triethylene ...glycol-functionalized thiolates while TEM images showed an average diameter of 5.4±1.3 nm. Solution UV–vis spectra of this new material in different alcohols present a shift of the surface plasmon band which is in accord with Mie theory. This suggests that the presence of a protecting monolayer able to interact with the solvent does not affect the optical properties of the gold core. These functional MPCs show a acid-induced formation of clusters which is time dependent and whose effect on the optical properties of the aggregate is solvent dependent.
Graphic
Background and aim
Circulating immune complexes of alpha-fetoprotein (AFP) and SCCA (squamous cell carcinoma antigen) with IgMs (AFP-IgM and SCCA-IgM, respectively) represent a promising new class of ...serum markers with diagnostic and prognostic value in the management of patients with hepatocellular carcinoma (HCC). The enhancement of diagnostic indexes for cancer detection achieved with combination of biomarkers by linear logistic regression has been demonstrated in several simulation studies on multiple diagnostic assays. The aim of the study was to evaluate the improvement of the diagnostic accuracy by combination of SCCA-IgM and AFP-IgM compared with the diagnostic accuracy of free AFP in sera of patients with HCC and cirrhosis.
Patients and methods
Serum samples from 81 patients with HCC (mean age ± SD: 63 ± 8 years; male patients 73%; HCV infected 52%; without any therapeutic treatment 50%) and 82 patients with cirrhosis (mean age ± SD: 53 ± 9 years; male patients 66%; HCV infected 68%) were collected. The logistic regression parameters were calculated on a previously published data set of 50 patients with HCC and 50 patients with cirrhosis, where the distribution of serum levels of SCCA-IgM and AFP-IgM in HCC patients was significantly different from that in patients with cirrhosis (Mann-Whitney U test, p<0.01). Serum levels of SCCA-IgM and AFP-IgM were assessed in parallel using the Hepa-IC and Hepa AFP-IC kits and AFP was determined by an automatic analyzer (ADVIA Centaur
®
, Siemens Diagnostics, Italy).
Results
The patients were stratified according to sex (male), HCV infection (positive) and therapeutic treatment (negative) to apply a linear logistic regression model using regression parameters calculated from a data set of a reference population. A subgroup of 30 patients with HCC and 41 patients with cirrhosis was analyzed. The diagnostic accuracy measured as the area under the ROC curve (AUC) for the SCCA-IgM and AFP-IgM assays was roughly the same, with a weak supremacy of AFP-IgM (AUC = 0.62), and was comparable with that of free AFP (AUC = 0.64). The gain in diagnostic accuracy achieved with the combination of SCCA-IgM and AFP-IgM levels by linear logistic regression was 14% (AUC = 0.71) compared with the diagnostic accuracy of AFP-IgM and 11% compared with that of free AFP. With the estimation of the partial AUC (pAUC0.3), an alternative measurement of AUC that takes into consideration only specificity rates with clinical relevance (specificity >70%), the highest improvement in accuracy for HCC detection was obtained, with an increase of up to 62% compared to pAUC0.3 of AFP-IgM and up to 23% compared to pAUC0.3 of free AFP.
Conclusion
The results demonstrate that the combination by linear logistic regression of biomarkers-IgM immune complexes improves the diagnostic accuracy for HCC detection using regression parameters calculated in a reference population with defined clinical characteristics. These results support the usefulness of devices based on a panel of non-overlapping biomarkers-IgM complexes, such as multi-marker biochips, increasing the sensitivity and maintaining a high specificity for HCC diagnosis compared with conventional single-marker assays.
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