Dynamic space structure of the Leu-enkephalin molecule in DMSO solution

Vesterman, B.; Saulitis, Juris; Betins, J.; Liepiņš, Edvards; Nikiforovich, Gregory V.

doi:10.1016/0167-4838(89)90274-4

Cited by 22 publications

(20 citation statements)

References 22 publications

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“…The results of this investigation indicated that the repeat region in CSP forms a stem-like superhelix. Although helical tendencies have not been established as a common trend present in all immunogenic peptides [24], strong correlations of immunogenicity and antigenicity with helix formation have been previously documented [10,25-28]. Despite the variations in structural tendencies observed for immunogenic peptides, which illustrate the diversity of the immune system, it is possible that peptides derived from the CSP are required to have helical structures to interact efficiently with their corresponding antibodies.…”

Section: Discussionmentioning

confidence: 99%

T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics

Topchiy

Armstrong²,

Boswell

et al. 2013

Malar J

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BackgroundT1BT* is a peptide construct containing the T1 and B epitopes located in the 5’ minor repeat and the 3’ major repeat of the central repeat region of the Plasmodium falciparum circumsporozoite protein (CSP), respectively, and the universal T* epitope located in the C-terminus of the same protein. This peptide construct, with B = (NANP)3, has been found to elicit antisporozoite antibodies and gamma-interferon-screening T-cell responses in inbred strains of mice and in outbred nonhuman primates. On the other hand, NMR and CD spectroscopies have identified the peptide B’ = (NPNA)3 as the structural unit of the major repeat in the CSP, rather than the more commonly quoted NANP. With the goal of assessing the structural impact of the NPNA cadence on a proven anti-plasmodial peptide, the solution structures of T1BT* and T1B’T* were determined in this work.MethodsNMR spectroscopy and molecular dynamics calculations were used to determine the solution structures of T1BT* and T1B’T*. These structures were compared to determine the main differences and similarities between them.ResultsBoth peptides exhibit radically different structures, with the T1B’T* showing strong helical tendencies. NMR and CD data, in conjunction with molecular modelling, provide additional information about the topologies of T1BT* and T1B’T*. Knowing the peptide structures required to elicit the proper immunogenic response can help in the design of more effective, conformationally defined malaria vaccine candidates. If peptides derived from the CSP are required to have helical structures to interact efficiently with their corresponding antibodies, a vaccine based on the T1B’T* construct should show higher efficiency as a pre-erythrocyte vaccine that would prevent infection of hepatocytes by sporozoites.

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Section: Discussionmentioning

confidence: 99%

T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics

Topchiy

Armstrong²,

Boswell

et al. 2013

Malar J

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“…Three sets of MD [29,30] runs were performed using AMBER94 force field. A dielectric constant of 45 was used, to simulate the DMSO environment.…”

Section: Molecular Dynamics (Md) Studiesmentioning

confidence: 99%

A putative bioactive conformation for the altered peptide ligand of myelin basic protein and inhibitor of experimental autoimmune encephalomyelitis [Arg91, Ala96] MBP87–99

Mantzourani

Tselios

Grdadolnik

et al. 2006

Journal of Molecular Graphics and Modelling

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“…It was found by using mass spectrometry that two different peptides were present with the sequence Tyr-Gly-Gly-Phe-[Leu/Met] in a ratio of 3 or 4 Met to 1 Leu (Hughes et al, 1975). Since this discovery, scientists have tried to determine the conformation of these peptides in different solvents such as water and dimethyl sulfoxide (DMSO), using spectroscopic techniques, predominantly nuclear magnetic resonance (NMR) spectroscopy, but also circular dichroism (CD) and Fourier transform-infrared (FTIR) spectroscopy (Khaled et al, 1977;Garbay-Jaureguiberry et al, 1977;Stimson et al, 1979;Higashijima et al, 1979;Gupta et al, 1986;Motta et al, 1987a,b;Gerothanassis et al, 1987;Surewicz and Mantsch, 1988;Glasser and Scheraga, 1988;Sakarellos et al, 1989;Vesterman et al, 1989;Picone et al, 1990; Moret et al, 1990;Gerothanassis et al, 1992;Graham et al, 1992;Doi et al, 1994). In 1977 Khaled et al found that some of the physical properties of Met-enkephalin (M-Enk) and Leu-enkephalin (L-Enk), such as proton and carbon chem-bonds and two salt bridges.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of Leu-enkephalin in water and DMSO

Spoel

Berendsen²

1997

Biophysical Journal

116

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The structure of Leu-enkephalin (L-Enk) and Met-enkephalin (M-Enk) have frequently been studied, in particular by nuclear magnetic resonance spectroscopy. After more than 20 years of research, it was concluded that enkephalins have no preferred structure in aqueous solution, but that they may have in other solvents. We have performed molecular dynamics simulations of zwitterionic L-Enk in water, and zwitterionic as well as neutral L-Enk dimethyl sulfoxide (DMSO). In water the peptide is very flexible, although there seems to be a preference for compact conformations. In DMSO, the peptide forms a clear salt bridge in the zwitterionic form, but has no preferred conformation in the neutral form. This difference in conformation may provide an explanation for measurements in DMSO in which multiple conformations were found to exist. In this paper we introduce a new formulation for a dihedral angle autocorrelation function, and apply it to study side-chain dynamics in L-Enk. We find that the side-chain dynamics of the large Tyr and Phe residues cannot be adequately sampled in 2.0-ns simulations, while this does seem to be possible for the smaller Leu side chain.

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Dynamic space structure of the Leu-enkephalin molecule in DMSO solution

Cited by 22 publications

References 22 publications

T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics

T1BT* structural study of an anti-plasmodial peptide through NMR and molecular dynamics

A putative bioactive conformation for the altered peptide ligand of myelin basic protein and inhibitor of experimental autoimmune encephalomyelitis [Arg91, Ala96] MBP87–99

Molecular dynamics simulations of Leu-enkephalin in water and DMSO

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