Sequence dependence in solid-phase-synthesis-cyclization-cleavage for Cyclo(-arginyl-glycyl-aspartyl-phenylglycyl-)

On‐resin head‐to‐tail cyclization of cyclotetrapeptides: optimization of crucial parameters

“…Moreover, the influence of the steric hindrance of different amino acids involved in the ring closure was evaluated. The synthesis of cyclo(Phg-Arg-Gly-Asp), previously reported as presenting cyclodimerization to some extent [37], dependent on the residues directly involved in the ring closure, was chosen as a model to compare the cyclization-cleavage methodology on an oxime resin with the on-resin head-to-tail cyclization strategy proposed in this paper.…”

“…Syntheses of cyclotetrapeptides by a solid-phase cyclization-cleavage strategy, based on intrachain aminolysis of the peptides, were described [35][36][37][38]. In particular, this approach was used by Nishino et al [37,38] for the preparation of cyclo(Arg-Gly-Asp-Phg), a cyclic tetrapeptide presenting an inhibitory activity toward cell adhesion. This study showed that the extent of oligomerization strongly depends on the choice of the C-terminal residue (from 20% of dimer when Phg is in the C-terminal position, to 40% with Gly).…”

“…A series of Arg-Gly-Asp (RGD) containing cyclotetrapeptides cyclo(Xaa-Arg-Gly-Asp) (Xaa = Ala, Phe, Phg, D-Ala, D-Phe, D-Phg) was chosen as model peptides. In particular, the synthesis of cyclo(Phg-Arg-Gly-Asp) was previously reported as presenting cyclodimerization to some extent [37,38]. Moreover, the RGD tripeptide is a universal cell-recognition sequence of several extracellular matrix proteins bound to integrins, which are involved in different important physiologically processes like cell differentiation, platelet aggregation and tumour metastasis.…”

Novel Cycloundecapeptides Related to Gramicidin S with Both High Antibiotic Activity and Low Hemolytic Activity

“…The protected linear precursors were prepared by using t-butoxycarbonyl (Boc)-solid phase peptide synthesis (SPS) on oxime resin (loading of oxime group: 0.35 mmol/g resins). [16][17][18] Leu residue as a C-terminal amino acid residue was used based on the propensity of the biosynthetic precursor of GS, tyrocidin (TA) and gratisin (GR) to form a conformation highly favorable for head-tail cyclization. 3,4) The formations of the cyclic peptides by the cyclization-cleavage of the linear precursors on oxime resin were performed in 1,4-dioxane with 2 eq of triethylamine and acetic acid for 1 d at room temperature.…”

Synthesis of Bicyclic Peptides

“…Removal of non-bridged failure sequences is, hence, simplified since after completion of the chain assembly and cleavage from the support, Cys-containing peptides may be captured to Cyscoated resin beads via disulfide bond formation. An alternative method to simplify the purification is anchoring the peptide chain to the support through one of the side chain functionalities that participates in the lactam formation [39]. The cyclization then triggers the cleavage from the support Scheme 11.…”