Synthesis of cyclic peptides on dual function supports

Flanigan, Everett; Marshall, Garland R.

doi:10.1016/s0040-4039(01)98240-1

Cited by 75 publications

(28 citation statements)

References 9 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Alcaro

Sabatino

Uziel

et al. 2003

Journal of Peptide Science

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Cyclotetrapeptides are constrained cyclic peptides whose synthesis is considered a difficult task. A methodology based on on-resin head-to-tail cyclization by anchoring the side chain of a trifunctional amino acid was investigated. A series of model cyclotetrapeptides containing the RGD sequence cyclo(Xaa-Arg-Gly-Asp) (Xaa = Ala, Phe, Phg, D-Ala, D-Phe, D-Phg) was synthesized with no cyclodimerization by-products. An evaluation and optimization study of all of the parameters directly involved in the ring closure was performed.

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Section: Introductionmentioning

confidence: 99%

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

Alcaro

Sabatino

Uziel

et al. 2003

Journal of Peptide Science

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“…Nearly all cyclic peptides synthesized to date have been obtained through ring closure in solution at high dilution. However, the preparation of N-terminal to C-terminal cyclized peptides has also been achieved by intramolecular aminolysis of peptide chains which were C-terminally linked to solid supports via active esters (10)(11)(12). Intramolecular sidechain to side-chain cyclizations on solid supports through disulfide bond formation between two half-cystine residues have also been reported (13,14).…”

mentioning

confidence: 99%

Synthesis of side‐chain to side‐chain cyclized peptide analogs on solid supports

Schiller

Nguyen

Miller

1985

International Journal of Peptide and Protein Research

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Cyclic peptide structures of the type ‐Lys‐R1—Rn‐Glu‐ can be synthesized on the Merrifield resin by assembling the peptide chain using Nα‐Fmoc‐amino acids and Boc and tert.‐butyl protection for the side‐chains of Lys and Glu, respectively. If residues R1 to Rn contain side‐chain functional groups, TFA‐resistant protection is required. After TFA treatment cyclization on the resin can be performed with appropriate coupling reagents. The formation of such cyclic structures may be preceded or followed by peptide chain assembly using Nα‐Boc‐amino acids and the entire peptide chain containing the cyclic portion is finally cleaved by HF treatment. Using this principle we synthesized the following opioid peptide related cyclic analogs: H‐Tyr‐d‐Lys‐Gly‐Phe‐Glu‐NH2 (I), H‐Tyr‐Lys‐Gly‐Phe‐Glu‐NH2 (II), H‐Tyr‐d‐Lys‐Phe‐Glu‐NH2 (III), H‐Tyr‐d‐Glu‐Gly‐Phe‐Lys‐NH2 (IV), H‐Tyr‐d‐Glu‐Phe‐Lys‐NH2 (V), H‐Tyr‐d‐Orn‐Gly‐Glu‐NH2 (VI) and H‐Tyr‐d‐Ala‐Lys‐Phe‐Glu‐NH2 (VII). Cyclic monomers were obtained in all cases, as demonstrated by mass spectrometry. Analysis of side‐products revealed a slow‐down of the HF deprotection of O‐benzylated tyrosine as a consequence of hydrophobic interactions as well as the formation of a side‐chain‐linked antiparallel cyclic dimer in the case of compound VI. In conclusion, the described method permits the convenient preparation of peptide analogs cyclized via amide bond formation between side‐chain amino and carboxyl groups in reasonable yield.

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“…The sulfur was oxidized to sulfone 2.10 [63] to enhance its sensitivity to nucleophilic attack. This linker has been used for the synthesis of cyclic peptides [97].…”

Section: Cleavage From the Resinmentioning

confidence: 99%