Synthetic
peptides mimicking the binding site of fertilin β
to its receptor, integrin α6β1, were shown to inhibit
sperm–egg fusion when added to in vitro media. In contrast,
the synthetic cyclic hexapeptide, cyclo(Cys1-Ser2-Phe3-Glu4-Glu5-Cys6),
named as cFEE, proved to stimulate gamete fusion. Owing to its biological
specificity, this hexapeptide could help improve the in vitro fertilization
pregnancy rate in human. In an attempt to establish the structure–activity
relationship of cFEE, its structural dynamics was herein analyzed
by means of ultraviolet circular dichroism (UV-CD) and Raman scattering.
The low concentration CD profile in water, containing mainly a deep
minimum at ∼202 nm, is consistent with a rather unordered chain.
However, an ordering trend of the peptide loop has been observed in
a less polar solvent such as methanol, where the UV-CD signal shape
is formed by a double negative marker at ∼202/215 nm, indicating
the presence of a type-II′ β-turn. Raman spectra recorded
in aqueous samples upon a 100-fold concentration increase, still showed
an important population (∼30%) of the disordered structure.
The structural flexibility of the disulfide bridge was confirmed by
the Raman markers arising from the Cys1-Cys6 disulfide bond-stretch motions. Density functional theory calculations
highlighted the formation of the type-II′ β-turn on the
four central residues of cFEE (i.e., -Ser2-Phe3-Glu4-Glu5-) either with a left- or with a
right-handed disulfide. The structure with a left-handed S–S
bond, however, appears to be more stable.
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