Using research results as a health promotion strategy: a five-year case study in Canada

Researchers in the field of health tend to share the resultsof their studies with colleagues by presenting papers and publishingin professional Journals. This practice is no longer adequateto promote major changes, as the infhiencers or agents of changesuch as senior administrators, elected officials and even thevoting public remain ignorant of the studies and their results.This article presents a case study of an effective, practicalhealth promotion strategy aimed at these agents of change. Itdescribes the planned, systematic dissemination of the resultsof two national surveys of the health knowledge, attitudes andbehaviour of schoolchildren in Canada. As a result, major influencesand changes have been documented in the development of programmes,resources and policies relevant to improved health educationin schools across Canada.     

Non coded Cα,α-disubstituted amino acids

The crystal and molecular structure of the fully protected dipeptide Boc-Val-(S)-α-MeSer-OMe has been determined by X-ray diffraction techniques. Crystals grown from ethyl acetate/n-pentane mixtures are tetragonal, space group 14₁, with cell parameters at 295 K of a= 15.307(2), c= 18.937(10)Å, V = 4437.1 ų, M.W. = 332.40, Z = 8, D_m= 0.99 g/cm³ and D_x= 0.995 g/cm³. The structure was solved by application of direct methods and refined to an R value of 0.028 for 1773 reflections with I≥3σ(I) collected on a CAD-4 diffractometer. Both chiral centers have the (S) configuration. The dipeptide assumes in the solid state an S shape. The urethane moiety is in the cis conformation, while the amide bond is in the common trans conformation. The conformational angles φ₁, ψ₁ of the Val and φ₂, and ψ₂ of the (S)-αMeSer fall in the F region of the φ-ψ map. The isopropyl side chain of the Val residue has the (t, g^?) conformation, while the Ser side chain has a g⁺ conformation. The hydrogen bond donor groups are all involved in intermolecular H-bond interactions. Along the quaternary axis the dipeptide molecules are linked to each other with the formation of infinite rows.     

Conformational characteristics of homo-oligopeptides of O-benzyl-L-tyrosine+

Conformational studies of X [-L-Tyr(Bzl)-]_n-series bound to polyethyleneglycol (X = H₂ Nps; n = 3–8) in the solid state and in solvents of different polarities and capabilities of forming hydrogen bonds are reported. By using i.r. absorption, the occurrence of the β-structure in the higher oligomers in the solid state was established. By means of i.r. absorption and CD the onset of that ordered conformation in solution was assessed as a function of chain length. The effects induced by the presence of the N-protecting group and added base, and by changing the nature of solvent on the conformational preferences of the [-L-Tyr(Bzl)-]_n homo-peptides were also examined. The 2-nitrophenylsulphenyl chromophoric derivative of the α-amino group is proposed as a circular dichroism sensor for β-structure in peptides.     

STUDIES ON THE COUPLING RATES IN LIQUID-PHASE PEPTIDE SYNTHESIS USING COMPETITION EXPERIMENTS

Competition experiments were carried out in order to determine relative reaction rates, V_rel for the peptide-forming step. Using the liquid-phase method of peptide synthesis a model system was developed to investigate the influence of coupling method, amino component, derivatization and solvent upon V_rel. According to a standard procedure, V_rel for all 20 commonly occurring amino acids were established. A strong dependence of V_rel upon steric effects of the coupling components was found. The data obtained may serve as a guideline for optimizing the reaction conditions in peptide synthesis.     

Conformational studies on host-guest peptides containing chiral α-methyl-α-amino acids

The conformational behaviour of host-guest peptides of the type Ac-Ala-Xxx-Ala-Ala-Xxx-Ala-Ala-Xxx-Ala-Ala-NH-PEGM (Xxx =α-aminoisobutyric acid (Aib), (S)-2-ethylalanine ((S)-Iva). (S)-2-methyiserine ((S)-α-MeSer)) has been studied by CD spectroscopy in CF₃CH₂OH. CH₃OH. and water and by i.r. spectroscopy in CHCl₃ and in the solid state. In this way the relative helix-inducing potential of the two chiral α-methyl-α-amino acids (S)-Iva and (S)-α-MeSer could be established in comparison to the strong helix-former Aib. The results show that (S)-Iva exerts a comparable helix-inducing effect as Aib, making this amino acid a valuable complementary tool for the stabilization or induction of helices. No significant helix-promoting effect was observed for (S)-α-MeSer in polar solvents; however, the i.r.-spectroscopic data in CHCl₃ and in the solid state point to a helical conformation under these conditions. Possible reasons for the different behaviour of (S)-Iva and (S)-α-MeSer are briefly discussed.     

Sequence-dependence of secondary structure formation

The conformational behaviour of the monodisperse amphiphilic oligopeptides (L-Thr-L-Val)_n (I and II) and (L-Ser-L-Leu)_n (III) for n = 1–4 was investigated by CD spectroscopy in TFE, MeOH and water. A conformational transition random-coil -> ß-structure was observed for both series: the critical chain length for ß-structure formation turned out to be dependent on solvent and spatial similarity of the amino acid side-chains. The very short critical chain-length for the onset of ß-structure formation for peptides I and II (n = 3) is explained by the formation of bilayer sheets, in which the minimization of hydrophobic contacts between the amphipilic peptide and the hydrophilic solvent represents an important driving force for ß-structure formation. The use of amphiphilic peptides for the construction of artificial proteins is briefly discussed.     

Sequence-dependence of secondary structure formation II*

The conformational influence of the insertion of two guest amino acids into a homooligopeptide consisting of L-Val residues was investigated by circular dichroism and infrared spectroscopy. L-Ala, L-Ile and L-Leu were chosen as guest amino acids and their β-structure disrupting properties studied with respect to size and symmetry of their side-chains. These studies were complemented by investigations concerning the aggregation behaviour of the various peptides by means of gel permeation chromatography. It is shown that the tendency of the various peptides to form β-structures and to aggregate increases with increasing similarity in the spatial size of the side-chains between guest and host amino acids. The impact of those results on the prediction of peptide secondary structure as well as their importance for peptide synthesis is briefly discussed.