O

Figure 32

a 14-membered hydrogen bond between the carbonyl of the C-terminus and the NH of the amide two residues toward the N-terminus (3 residues per turn) (Fig. 33) [60]. Seebach's y-peptides formed a 14-membered hydrogen bond between the carbonyl of the N-terminus and the carbonyl two residues toward the C-terminus (2.6 residues per turn) [61].

Of the many elegant studies reported by Gellman and coworkers, two are particularly relevant to the discussion at hand. The first was the formation of water-soluble ยก-amino acid hexamers with stable helices in water [62]. Four different systems containing positively charged amine functionalities were prepared (Fig. 34). The charge promoted water solubility and, at the same time, prevented aggregation [63]. Structural analyses using the aforementioned techniques confirmed that these oligomers adopted a 14-helix conformation in aqueous solution. Demonstrating that conformationally stable, water-soluble candidates could be prepared was the first step toward using these new materials to solve biologically relevant problems.

The Gellman laboratories later reported the chemical synthesis of a 17-mer based on the 12-helix forming fraras-2-aminocyclopentanoic acids [64]. Charged amine functionalities in combination with neutral monomer units were incorporated into the oligomer to provide an amphiphilic secondary structure (Fig. 35). When tested for bactericidal and bacteriostatic activity against a vancomycin-resistant bacterial strain, this material exhibited activity similar to that of a known 23-mer a>

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