Cyclododecapeptide analog of the polyhexapeptide of elastin: 2‐D NMR and molecular dynamics studies

The hexapeptide, (APGVGV), is one of the repeating sequences found in the natural protein, elastin. The cyclododecapeptide, cyclo( L ‐Ala 1 – L ‐Pro 2 –Gly 3 – L –Val 4 –Gly 5 – L ‐Val 6 ) 2 , was synthesized and was found to undergo an inverse temperature transition leading to crystallization. Extensive NMR experiments have been carried out previously to evaluate its secondary structure in comparison to that of its linear counterpart, polyhexapeptide (APGVGV) n , directly and in terms of the concept of cyclic conformations with linear conformational correlates. Building on the previous work, this report adds 2‐D NMR and molecular dynamics studies on the molecular structure of the cyclododecapeptide. From the 2‐D COSY and 2‐D NOESY experimental results, a reversal of the previous Gly 3 and Gly 5 resonance assignments in the cyclododecapeptide is reported. And in the 2‐D NOESY study, a prominent NOE is found between the NH's of the two valine residues at position 4 and 6. Because the Val 4 and Val 6 residues are not adjacent to each other sequentially, the proximity of these two backbone hydrogens is used as an imposed constraint in constructing the molecular structure of the cyclododecapeptide. Molecular dynamics investigations were employed using the information from the 1‐D and 2‐D NMR experiments to arrive at potential molecular structures of the cyclododecapeptide. The characteristic secondary structural feature obtained is the expected Type II Pro 2 –Gly 3 β‐turn consisting of the 10‐membered hydrogen bond between the residue‐4 NH and the residue‐1 CO, a feature previously found in this and all other repeating peptides in elastin which contain the Pro 2 –Gly 3 sequence.