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Methods of peptide conformation studies

100%

Bierzynski A.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

In solution most of the peptides assume multiple flexible conformations. Determination of the dominant conformers and evaluation of their populations is the aim of pep- tide conformation studies, in which theoretical and experimental methods play complementary roles. Molecular dynamics or Monte Carlo methods are quite effective in searching the conformational space accessible to a peptide but they are not able to estimate, precisely enough, the populations of various conformations. Therefore, they must be supplemented by experimental data. In this paper, a short review of the experimental methods, most widely used in peptide conformational studies, is presented. Among them NMR plays the leading role. Valuable information is also obtained from hydrogen exchange, fluorescence resonance energy transfer, and circular dichroism measurements. The advantages and shortcomings of these methods are discussed.

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Solution structure of conformationally restricted vasopressin analogues

63%

Trzepalka E., Oleszczuk M., Maciejczyk M., Lammek B.

Acta Biochimica Polonica

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2004

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tom 51

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nr 1

In recent years, a massive effort has been directed towards designing potent and selective antagonists of neurohypophyseal hormones substituted at position 3. Modification of vasopressin at position 3 with 4,4'-biphenylalanine results in pharmacologically inactive analogues. Chemically, this substitution appears to vary only slightly from those previously made by us (1-Nal or 2-Nal), which afforded potent agonists of V2 receptors. In this situation, it seemed worthwhile to study the structure of the analogues with 4,4-biphenylalanine (BPhe) at position 3 in aqueous solution using NMR spectroscopy and total conformational analysis. This contribution is part of extensive studies aimed at understanding spatial structures of 3-substituted [Arg8 ]vasopressin analogues of different pharmacological properties. NMR data were used to calculate 3D structures for all the analogues using two methods, EDMC with the ECEPP/3 force field, and molecular dynamic with the simulated annealing (SA) algorithm. The structures obtained by the first method show a better fit between the NMR spectral evidence and the calculation for all the peptides.

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Voltage activated ion channels formed by a synthetic alpha-helical peptide: - Determination of channel stoichiometry and molecular modelling of peptide conformation

51%

Mellor I. R., Kerr I. D., Sansom M. S. P., Sukumar M., Balaram P.

Cellular and Molecular Biology Letters

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1996

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tom 01

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nr 3

We designed and synthesized an 18 residue peptide (MS 18) similar to the channel forming fungal antibiotic alamethicin. MS18 formed ion channels in lipid bilayers exhibiting a low discrete conductance level of 55 pS and brief openings to many other conductance levels. Channel formation was markedly dependent on transbilayer voltage with macroscopic conductance increasing exponentially beyond an activation voltage. The activation voltage was higher for lower concentrations of peptide. The relationship between conductance, voltage and peptide concentration was used to calculate the mean number of peptide monomers forming the MS18 channel. This gave an estimate of 4 MS18 monomers per channel. Molecular modeling of MS18 revealed a predominantly α-helical structure.

Ograniczanie wyników

2 Acta Biochimica Polonica

1 Cellular and Molecular Biology Letters

1 Balaram P.

1 Bierzynski A.

1 Kerr I. D.

1 Lammek B.

1 Maciejczyk M.

1 Mellor I. R.

1 Oleszczuk M.

1 Sansom M. S. P.

1 Sukumar M.

1 Trzepalka E.

1 2004

1 2001

1 1996

Methods of peptide conformation studies

Solution structure of conformationally restricted vasopressin analogues

Voltage activated ion channels formed by a synthetic alpha-helical peptide: - Determination of channel stoichiometry and molecular modelling of peptide conformation