Turn Elements and Hairpins

The last class of secondary structures that will be discussed here are turn elements, of which hairpins will receive the major attention. Van Esch, De Feyter, and coworkers have studied the folding and adsorption of small molecules 1315 that mimic turn elements (Fig. 13.16) [36]. These turn mimics consist of a cat-echol unit and two alkyl chains, both containing an amide group for additional stabilization of the folded conformation by intramolecular hydrogen bonding. Molecular modeling predicted that folding depends strongly on the length of the spacers between the catechol moiety and the amide groups. Indeed, compound 13 with spacers of equal length did not adsorb in the folded conformation as found by STM analysis since this conformation is rather twisted than flat, rendering adsorption of the folded structure unfavorable. On the other hand, compounds 14 and 15 with spacers differing by one methylene group did adsorb in the folded conformation, and especially 15 yielded highly ordered monolayers at the solid-liquid interface. This study shows that, in addition to the factors discussed above, the 'flatness' of the folded conformation, encoding for maximum interaction with the flat substrate surface, can determine whether the compound adsorbs in the folded or unfolded conformation.

In related peptide work, Kelly, Powers, and coworkers have studied the self-assembly of b-hairpin peptide 16 at interfaces employing various techniques (Fig. 13.18) [37-40]. Peptide 16 consists of two strands with alternating hydrophobic and hydrophilic residues linked by a D-Pro-Gly b-turn and labeled with a fluorophore (DMBDY). CD measurements showed that this water-soluble peptide adopts a random coil conformation in deionized water [37]. However, it spontaneously adsorbs at the air-water interface as indicated by fluorescence microscopy. The surface pressure isotherms of the formed monolayers have been studied and LB films have been deposited on mica substrates [38]. The observed area per molecule and the pattern in the monolayer on mica as observed by AFM are in good agreement with adsorption of the peptide in the folded state, i.e. a hairpin conformation (Fig. 13.18). The derived structural model was further supported by a neutron reflection study. A later study revealed that the SAMs at the air-water in-

Fig. 13.17 Structure and concept of turn mimics 13-15 (top left) and STM images of the adsorbed turn elements on HOPG [36].

Fig. 13.18 Hierarchical self-assembly ofb-hairpin peptide 16 containing a DMBDY fluorophore (left) in tapes as shown by the AFM image on mica and the corresponding structural analysis [38]. (Reproduced from ref. [38] with permission.)

Fig. 13.18 Hierarchical self-assembly ofb-hairpin peptide 16 containing a DMBDY fluorophore (left) in tapes as shown by the AFM image on mica and the corresponding structural analysis [38]. (Reproduced from ref. [38] with permission.)

terface are stabilized by the DMBDY fluorophores and the D-Pro-Gly b-turn elements [39]. This might be due to van der Waals forces between the DMBDY fluo-rophores and between the hydrophobic turn elements. Moreover, it was found that at higher pH or higher salt concentration as compared to deionized water, the glutamic acid residues could get deprotonated resulting in destabilization of the monolayer at the air-water interface. While it becomes apparent that the folding and adsorption of these hairpins is governed by different types of interactions and that specific conditions are required, clearly folding is facilitated by adsorption, probably due to lowering of the nucleation barrier.

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