Synthesis of a new type of cyclic peptide: a bicyclic nonapeptide

Conformation and calcium-binding properties of a bicyclic nonapeptide

“…Model peptide BCP2 belongs to a series of synthetic bicyclic peptides designed to point out, in a systematic way, the structural features suitable for calcium binding by peptide systems 7–10. In this paper a BCP2 titration with calcium ions, together with a detailed analysis of the conformational behavior of the peptide, both in its free and calcium‐loaded form, performed by means of NMR techniques, are presented.…”

“…The present paper reports the NMR structural characterization of BCP2,6 a bicyclic homodetic nonapeptide of sequence cyclo ‐(Glu 1 –Ala 2 –Pro 3 –Gly 4 –Lys 5 –Ala 6 –Pro 7 –Gly 8 )– cyclo ‐(1γ → 5ϵ) Gly 9 , both in its free and calcium‐loaded forms, and provides a restrained molecular dynamics (RMD) molecular model for the equimolar complex. BCP2 does not reproduce any natural system; it belongs to a series of synthetic peptides, designed to study, in a systematic way, the structure requirements for calcium binding polypeptides 7–10. Due to both its sequence and architecture, built of three equal‐length branches, BCP2 is a highly symmetric system.…”

Synthesis of Bicyclic Peptides

“…Second, two pairs of side-chain functionalities may be pair wise connected with amide or disulfide bonds (7)(8)(9). Third, two side-chain cyclized monocyclic peptides can be connected by a disulfide bridge (10) or the two peptides, at least one of which is a cyclized one, are tethered to each other via two intermolecular disulfide bridges (11). If the structure is constructed entirely by amide bonds, the peptide is called homodetic.…”

“…Numerous this kind of peptides exhibiting varying degree of ring flexibility have been constructed, using naturally occurring trifunctional amino acids, usually Lys and Glu, as branching units [10,11]. Scheme 1 depicts the original convergent strategy applied to the solution-phase synthesis of such peptides.…”

Bicyclic peptides as models of calcium binding sites: Synthesis and conformation of a homodetic undecapeptide

“…Indeed, it is essentially based on the appropriate placement of calcium‐coordinating residues in a bicyclic peptide structure. It has been proposed that bicyclic peptides can mimic the three‐dimensional structure of protein sites better than linear or monocyclic analogs 22–27…”