X-ray Crystallographic Structure of an Artificial β-Sheet Dimer

This paper describes the X-ray crystallographic structure of a
designed cyclic β-sheet peptide that forms a well-defined hydrogen-bonded
dimer that mimics β-sheet dimers formed by proteins. The 54-membered
ring macrocyclic peptide (1a) contains molecular template
and turn units that induce β-sheet structure in a heptapeptide
strand that forms the dimerization interface. The X-ray crystallographic
structure reveals the structures of the two “Hao” amino
acids that help template the β-sheet structure and the two δ-linked
ornithine turn units that link the Hao-containing template to the
heptapeptide β-strand. The Hao amino acids adopt a conformation
that resembles a tripeptide in a β-strand conformation, with
one edge of the Hao unit presenting an alternating array of hydrogen-bond
donor and acceptor groups in the same pattern as that of a tripeptide β-strand.
The δ-linked ornithines adopt a conformation that resembles
a hydrogen-bonded β-turn, in which the ornithine takes the place
of the i+1 and i+2 residues. The
dimers formed by macrocyclic β-sheet 1a resemble
the dimers of many proteins, such as defensin HNP-3, the λ-Cro
repressor, interleukin 8, and the ribonuclease H domain of HIV-1 reverse
transcriptase. The dimers of 1a self-assemble in the
solid state into a barrel-shaped trimer of dimers in which the three
dimers are arranged in a triangular fashion. Molecular modeling in
which one of the three dimers is removed and the remaining two dimers
are aligned face-to-face provides a model of the dimers of dimers
of closely related macrocyclic β-sheet peptides that were observed
in solution.