Linearization of the circular
peptide Kalata B1
Cyclic peptides can be linearized by breaking of a peptide
bond, usually in solvent accessible loops. Structure and stability
of the linear peptide give informations on the importance of
the loops in the folding and the stability of the circular peptide.
Such linearizations are similar in spirit to the circular permutations
performed on non-cyclic peptides (see below).
Six different linear analogs of the cyclic peptide Kalata B1
have been synthesized [Daly
& Craik, 2000]. Four linear peptides are able to fold
correctly indicating that the broken loops are not essential
for folding. It is shown that the two linear peptides that do
not fold correspond to peptides in which the disulfide macrocycle
typical of the Knottins has been disrupted. This highlight the
importance of the knot in Knottins.
Circular permutation of EETI-II
A similar approach has been applied to the non-cyclic EETI-II
Knottin [Chiche, Heitz & Strub, unpublished results]. In
such cases the native termini of the peptide are linked by a
regular peptide bond (usually with addition of a short peptide
link), and new termini are introduced somewhere else in the peptide
resulting in true circular permutations. Here the C- and N-termini
are connected with addition of three glycines and the 17-18 peptide
bond has been cleaved. The resulting permuted peptide has been
shown to fold correctly, indicating that the 16-19 β-turn
is not essential for folding.