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

Abstract

The solution conformations of the all l‐α‐peptide 1 and the corresponding retro‐all d‐α‐peptide 2, two 20‐meric peptides which generate antibodies that cross‐react with the gp120 envelop protein of human immunodeficiency virus‐1 (HIV‐1), have been investigated by high‐field H 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‐α‐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‐α‐peptide 1 and its retro‐inverso isomer 2 provide important insight into the conformational influences of the C‐ and N‐end group with l‐α‐ and retro‐l‐α‐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.

Global chain properties of an all l‐α‐eicosapeptide with a secondary α‐helix and its all retro d‐inverso‐α‐eicosapeptide estimated through the modeling of their CZE‐determined electrophoretic mobilities

“…depicting g f as a function of pH shows that within the range 2 < pH <3, both peptides are in the HC regime, where the formation of HZ and also the generation of a secondary structure are found. These results are consistent with NMR and circular dichroism experimental data reported in at around pH 2.3. In the HC regime, Peptide 1 has a g f higher than Peptide 2 indicating that the friction coefficients of these particles are not necessarily equal (different qualities of their BGE components chain interactions) although their changes with pH follow quite similar pathways until around pH 3 where both peptides enter the CG regime.…”

“…These experimental results clearly indicate the high sensitivity of CZE methods to detect different structural characteristics between a natural l ‐α‐peptide and its retroinverso isomer in the framework of molecular mimicry. In addition from , it was clear that both Peptides 1 and 2 included a secondary α‐helix structure at pH 2.3 in several solvents and aqueous BGE. These results were demonstrated through NMR and circular dichroism spectroscopy methods.…”

“…Within this brief context, this work has the purpose to estimate global chain properties at different pHs of the following peptides studied in (see also Supporting Information Table 1): (i) the all l ‐α‐eicosapeptide DDALYDDKNWDRAPQRCYYQ forming a secondary α‐helix from 6th to 13th amino acid residues (designated Peptide 1), (ii) the corresponding all retro‐ d ‐inverso‐α‐eicosapeptide QYYCRQPARWNKDDYLADD of Peptide 1 (designated Peptide 2), (iii) the fragment of Peptide 1 where the last Y is missing (designated Peptide 3), (iv) the fragment of Peptide 1 where the terminal strand RCYYQ is absent (designated Peptide 4), and (v) the fragment of Peptide 1 where the initial strand DDALY is absent (designated Peptide 5). Peptide 1 is within the group of immunogenic peptides that react with the coat protein of human immunodeficiency virus HIV‐1 gp120 in biochemical assays . The proposal is carried out on the base of our previous works concerning the modeling of of peptides and proteins .…”

Research Letter: Retroinverso Mimetics of S Peptide

“…There are many reports (6–12) exemplifying RI peptides possessing cross reactivity with an antibody against pro‐peptide antigens. There are other reports describing RI analogs that fail to mimic the biological properties the parent peptide (13,14).…”

Interaction Energy Analysis of Peptide can Predict the Possibilities of Mimetics by its Retroinverso Isomer

“…The RI analogs have been reported to mimic the antigen peptides of human immunodeficiency virus (HIV) (15), influenza virus (16), foot‐and‐mouth disease virus (FMDV) (3), histone H3 (17), p53 (18), etc. Opiate peptides also can be mimicked by their RI analog (10).…”