The conformational change of the model peptide Ac-K-G-R-G-D-G-amide induced by a phospholipidic interface was investigated by proton nuclear magnetic resonance (1H NMR). In aqueous solution, the free peptide is highly flexible and disordered, even in the presence of deuterated dodecyl-phosphocholine (DPC-d38) micelles which mimic a membrane interface. The lipopeptide, obtained by grafting a lipid anchor [2,3-dipalmitoyl-D-(+)-glyceric acid] to the lysine side chain of the peptide, was studied by standard 2D 1H NMR spectroscopy combined with distance geometry and simulated annealing calculations. When anchored to a micelle interface, the peptide acquires a definite turn (II/I') conformation. We were also able to describe precisely the conformation of the diacylglyceric fragment of the lipopeptide in a lipid environment and to establish the average orientation of the peptide segment with respect to the micelle surface.

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A 32 residue peptide, Ac-AQWDADELRAAMKGLGTDEDTLIELASRTNK, spanning the first helix-loop-helix motif of the second repeat of human annexin I, was synthesized and studied by standard 2D proton NMR and molecular modeling. The peptide was solubilized either in aqueous solution, in TFE-H2O mixtures or in aqueous phospholipidic micellar solution. In pure aqueous solution, elements of helix secondary structure were observed. Addition of TFE led to a dramatic cooperative effect on the secondary structure with a very low transition midpoint indicative of the strong tendency of the peptide to form alpha helices. Only in the aqueous micellar solution was the full helix-loop-helix motif obtained, showing again the potency of a membrane-like micellar environment to initiate peptide secondary structures and even elements of tertiary structure. There were sufficient NMR data to perform molecular modeling of the structure of the annexin fragment solubilized in the presence of micelles. However, this structure showed a relatively high degree of flexibility, especially around the T17-D18 hinge at the end of the loop.

The solution conformation of a synthetic 18 amino acid peptide derived from a consensus sequence of Annexins has been investigated by 1HNMR. Full sequential assignment has been achieved. Conformational properties of the peptide were deduced from the analysis of J(NH–CHα) coupling constants, amide proton exchange, 2D NOESY connectivities and computer modeling.

We present proton and phosphorus NMR data, which contribute to explain why the 5-methylcytidine (m5C) differently affects the conformational transitions of CGUAm5CG (Bloch et al., FEBS Letters 219, 464 (1987)) and CGm5CGCG (Ceolin et al., J. Am. Chem. Soc. 109, 2539 (1987)). The atypical intermediate form observed in the random coil to A-like duplex transition of CGm5CGCG is determined: this original duplex structure exhibits a frame-shift pairing of the two strands, with a partial conservation of the A-type structure. In the case of CGUAm5CG such a pairing process would lead to a complete mismatch pairing. This feature probably explains that the NMR data of CGUACG and CGUAm5CG are similar and consistent with a random coil to A-type helix transition. Nevertheless a significant difference between the correlation times observed for the molecular motions of the two duplexes is detected. Another example of unusual conformational transition of methylated RNA oligomers is given by CAm5CGUG.