Conformational Mobility of the Pyrrolidine Ring of Proline in Peptides and Peptide Hormones as Manifest in Carbon 13 Spin-Lattice Relaxation Times

Abstract The spin-lattice relaxation times (T1) of carbon 13 in natural abundance were determined for proline, N-acetyl-prolineamide, glycylproline, cyclo(triprolyl), and a series of proline-containing peptide hormones. The data are interpreted in terms of rapid interconversion of proline between various ring-puckered forms. The nature of the puckering depends upon the type of group attached to proline. In proline, the β, γ, and δ carbon atoms are appreciably more mobile than the α carbon atom, suggesting rapid interconversion between a number of ring-puckered forms. In melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) and its dimethylamido analog, the γ carbon atom has the greatest mobility, suggesting a rapid endo-exo interconversion at this position. In Gly-Pro and in acetyl-Pro-NH2, the cis and trans conformers of proline have very similar T1 values, indicating very little dependence of the dynamic proline ring conformation on the conformation at the peptide bond; in both isomers, the proline ring interconverts rapidly between half-chair conformers puckered at Cβ and Cγ. In thyrotropin-releasing hormone (lGlu-His-Pro-NH2), the proline ring conformation is similar to that in Gly-Pro, and independent of the state of ionization of the histidine residue. Oxytocin [see PDF for equation] , lysine-vasopressin [see PDF for equation] , [Ile5]angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe), and luteinizing hormone-releasing hormone ( lGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) all have proline in the trans conformation about the peptide bond, and the δ carbon atom has a mobility comparable to that of the α carbon atom. The latter reflects severe steric constraints at Cδ due to the neighboring residues. In oxytocin and angiotensin II, the β carbon atom is considerably more mobile than Cα or Cδ. In luteinizing hormonereleasing hormone, the proline ring apparently undergoes rapid interconversion between half-chair forms puckered at Cβ and Cγ, whereas in lysine-vasopressin, the mobility of Cγ is greatest

Determination of the Structure and Conformation of Bacterial Polysaccharides by Carbon 13 Nuclear Magnetic Resonance STUDIES ON THE GROUP-SPECIFIC ANTIGENS OF NEISSERIA MENINGITIDIS SEROGROUPS A AND X

Abstract The application of carbon 13 nuclear magnetic resonance to analysis of some phosphorylated acetamidohexose-containing meningococcal polysaccharides is described. A complete assignment of the spectra of both the serogroup A and X polysaccharides has been made. In addition the spectrum of a structurally related 1 →6-α-linked 2-acetamido-2-deoxy-d-glucose phosphate polysaccharide from Staphylococcus lactis NCTC 2102 has also been completely assigned. This has resulted in the structural elucidation of the serogroup X polysaccharide as a homopolymer of 2-acetamido-2-deoxy-d-glucopyranose, linked by 1→4-α-phosphodiester bonds. In addition, the O-acetyl substituents of the serogroup A polysaccharide have been located at C-3 of approximately 70% of the repeating units (1→6-α-linked 2-acetamido-2-deoxy-d-mannopyranose phosphate) of the homopolymer. Preliminary conformational information was also obtained from the large three-bond couplings between 31P and 13C (3J3131p-1313c), indicative of highly extended backbone formations

Gerschenkron revisited: The new corporate Russia

© 2015, Journal of Economic Issues / Association for Evolutionary Economics. Our analysis is based on firm-specific data compiled from the Russian Trading System stock exchange and SKRIN (CKP-H in Russian) database. We seek to identify the factors behind Russias dramatically improved corporate sector performance from the beginning of the 2000s to December 2007. We argue that improved long-term corporate performance was a consequence of several policy initiatives associated with the state-dominated banking sector, which enabled statesubsidized investment funds to be channeled from a structurally reengineered energy sector to targeted investment projects located in other industries. We claim that Russias industrial strategy closely conforms to Alexander Gerschenkrons catch-up theory

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Direct observation of molecular ordering of cholesterol in human erythrocyte membranes

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The molecular dynamics of cholesterol in bilayer membranes: A deuterium NMR study

The 2H-NMR spectra of selectively deuterated cholesterol, intercalated in egg phosphatidyl-choline, were examined. The orientation of the axis of motional averaging was calculated using the observed quadrupole splittings and the atomic coordinates. With the known orientation of the rotation axis, quadrupole splittings observed for deuterium labels on cholesterol can be related to the molecular order parameter of the sterol. In addition, knowledge of the axis orientation allows prediction of the magnitudes of quadrupole splittings for deuterium at other positions, which is useful in the choice of labelling for particular applications. Finally, preliminary relaxation time measurements yield information on the rates of anisotropic motion of cholesterol in bilayer membranes.Peer reviewed: YesNRC publication: Ye