[NMR paper] Comparison of the solution conformations of a human immunodeficiency virus peptidomim

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Comparison of the solution conformations of a human immunodeficiency virus peptidomimetic and its retro-inverso isomer using 1H NMR spectroscopy.

Related Articles Comparison of the solution conformations of a human immunodeficiency virus peptidomimetic and its retro-inverso isomer using 1H NMR spectroscopy.

J Pept Res. 1997 Dec;50(6):421-35

Authors: Higgins KA, Bicknell W, Keah HH, Hearn MT

The solution conformations of the all L-alpha-peptide 1 and the corresponding retro-all D-alpha-peptide 2, two 20-metric peptides which generate antibodies that cross-react with the gp 120 envelop protein of human immunodeficiency virus-1 (HIV-1), have been investigated by high-field 1H NMR spectroscopy. Complete sequential and inter-residue interaction assignments were made from the 2D NMR spectra acquired at 500 MHz and 600 MHz in 40% deuterotrifluoroethanol (d3-TFE)/H2O at pH 2.3, and in 300 mM sodium dodecyl sulphate (SDS) in 100% D2O or 90% H2O/10% D2O at pH 2.6. Based on analysis of the nuclear Overhauser effect (NOE) and amide exchange data, peptide 1 and its retro-inverso isomer 2 in the polar solvent environment of 40% d3-TFE/H2O at pH 2.3 show very similar topological features. However, in the relatively non-polar 300 mM SDS micellar environment, peptides 1 and 2 exhibit differences in their solution structures in terms of the amide backbone and side-chain orientations. In particular, under the SDS micellar condition, peptide 1 maintains much of the secondary structure observed for this 20-mer peptide in 40% d3-TFE/H2O, pH 2.3, whereas peptide 2 adopts a more extended structure. These NMR results provide the first confirmation that the secondary structure of the all L-a-peptide 1 is maintained in both polar and non-polar environments, whereas the secondary structure and topology of the notionally equivalent retro-inverso isomer depends more on the solvent conditions. These results with the all L-a-peptide 1 and its retro-inverso isomer 2 provide important insight into the conformational influences of the C- and N-end group with L-alpha- and retro-D-alpha-isomer pairs in non-polar environments, and thus have general relevance to the design of bioactive retro-inverso peptidomimetic analogues related to immunogenic or hormonal peptides.

PMID: 9440043 [PubMed - indexed for MEDLINE]



Source: PubMed