Loss of Helicity upon Adsorption

The examples provided above show that helical structures can adsorb at interfaces, while preserving (or even increasing) their helical content. However, many foldamers adopt a helical conformation in solution, which is (partially) lost when adsorbed at interfaces. Burkett and Read have synthesized a series of peptides, consisting of anionic aspartate, uncharged alanine, and cationic arginine segments. They investigated the helical conformational behavior in solution and at anionic and cationic colloidal silica substrates by CD and 1H-NMR spectroscopy

[18]. It appeared that the peptide helices showed partial unwinding upon adsorption at both substrates to maximize the number of complementary interactions between charged side chains of the peptide and the nearby opposite surface charges. An in-depth study of one of these peptides provided some remarkable insights [19]. The helices were oriented to the substrate with the complementary charged block. However, it was not necessarily the block oriented to the substrate that showed loss of helicity. Adsorption at both anionic and cationic colloids gave rise to loss of helicity in the arginine segment, while the alanine segment showed only partial helicity loss and the aspartate segment retained its helical conformation completely. In addition, heating of the helix-containing solution gave rise to loss of helicity mainly at the arginine terminus and to a lower extent at the aspartate terminus, whereas no loss of helicity was observed in the alanine segment. It should be noted that in these peptides, the strong dipolar charge distribution of the side chains is complementary to the backbone dipole, thereby stabilizing the helix. Apparently, charge compensation of one of the segments disturbs the intermolecular helix-forming interactions in such a way that the transition to the random coil structure will start and propagate from the less stable terminus. As indicated by the solution phase temperature study, the arginine segment represents the less stable terminus potentially due to a high nucleation barrier, which is further increased upon adsorption.

Another example of helical peptides that have lost helicity upon adsorption at interfaces is reported by Vankann, Hocker, and coworkers [20]. These peptides were built from a leucine-based hydrophobic segment and a hydrophilic head group composed of polar amino acids, e.g. 7 (Fig. 13.8), or oligo(ethylene oxide). The conformational preferences of the peptides were studied by CD spectroscopy both in solution and embedded in liposome lipid bilayers. In the lipid bilayer, the longer peptides retained their helicity to 'fit' in the layer, whereas the shorter peptides unfolded to form b-sheet structures. The peptides were also studied at the air-water interface with a Langmuir balance. The secondary structure of the adsorbed peptides was governed by the size of the head groups. The

7 Fmoc-Leun-Lyss-Tyr

Fig. 13.8 Amphiphilic peptide 7 adopts an a-helical conformation (left) when spread at the air-water interface; however, when the monolayer is compressed the peptide adopts an extended b-sheet conformation (right) [20]. (Reproduced in part from ref. [20] with permission.)

a-Helix

Fig. 13.8 Amphiphilic peptide 7 adopts an a-helical conformation (left) when spread at the air-water interface; however, when the monolayer is compressed the peptide adopts an extended b-sheet conformation (right) [20]. (Reproduced in part from ref. [20] with permission.)

peptides with bulky head groups were assumed to assemble as a-helices perpendicular to the surface, whereas the less dense packing of peptides without bulky head groups suggests a change of conformation into a b-sheet. Compression of the monolayers of 7 led to a conformational change from a-helix to b-sheet (Fig. 13.8), which could be inhibited by the use of the bulky oligo(ethylene oxide) groups. This example shows that the secondary structure of peptides can be governed by the way in which the folded structure 'matches' its surrounding, more than it is determined by intramolecular interactions.

Was this article helpful?

0 0

Post a comment