Z-Ala-Ile-OH, a dipeptide building block suitable for the formation of orthorhombic microtubes

Abstract

Self-assembling dipeptides have emerged in the last two decades as promising building blocks for the development of novel biomaterials. Among the various classes of dipeptides, aromatic dipeptides and especially diphenylalanine (Phe-Phe), which forms hexagonal nanotubes, have been the most extensively studied. However, aliphatic peptides or mixed aromatic-aliphatic dipeptides seem just as promising, exhibiting various structures ranging from amyloid fibrils to microtubes. Herein we report the single-crystal structure of an aliphatic dipeptide, alanine-isoleucine (Ala-Ile), C₁₇H₂₄N₂O₅, protected with a benzyloxycarbonyl (Z) group at the N-terminus. The protected dipeptide crystallizes in the orthorhombic space group P2₁2₁2₁ and forms hollow microtubes with orthorhombic symmetry upon evaporation on glass surfaces, as shown by field emission scanning electron microscopy (FESEM). These findings provide an increased understanding of the correlation between the single-crystal structure of the peptide building block and its self-assembly mechanism, and expand the library of available building blocks for microtechnological applications.

Keywords: Z-protection group; alanine; chiral peptide; crystal structure; hydrogen bonding; isoleucine; microtube.

Figure 1

FESEM images of the Z-Ala–Ile microtube assemblies after incubation in aqueous solution for 24 h and subsequent deposition on a glass slide. (a) Hollow microtubes emanate from the surface, (b) higher resolution image of a hollow microtube tip shows a layered substructure and (c) a view of a full microtube.

Figure 2

The mol­ecular structure of Z-Ala–Ile-OH, showing 50% probability displacement ellipsoids (Farrugia, 2012 ▸). For clarity, the residue abbreviations Z, Ala and Ile are also included.

Figure 3

Hydrogen bonding of Z-Ala–Ile-OH, viewed approximately along the a axis. Hydrogen bonds are shown as dashed lines in cyan with the donor–acceptor distances (D⋯A) in Å.

Figure 4

Wall-eyed stereoview of the crystal packing of Z-Ala–Ile-OH, viewed approximately along the a axis. Different colours denote mol­ecules related by space-group symmetry. Hydrogen bonds are shown as dashed lines in cyan.