145190-76-7Relevant academic research and scientific papers
Synthesis of cyclic peptides through hydroxyl side-chain anchoring
Yan, Liang Z.,Edwards, Patrick,Flora, David,Mayer, John P.
, p. 923 - 925 (2004)
A general method was developed for the synthesis of serine or threonine containing cyclic peptides utilizing the β-hydroxyl side-chain of these residues as an anchor point to Wang resin. The peptide chain was assembled by conventional Fmoc/tBu solid-phase chemistry followed by palladium catalyzed exposure of the allyl protected C-terminus group and on-resin cyclization. The cyclic heptapeptide stylostatin 1 was prepared to demonstrate the utility of this technique.
Direct Peptide Cyclization and One-Pot Modification Using the MeDbz Linker
Gless, Bengt H.,Olsen, Christian A.
, p. 10525 - 10534 (2018)
The one-pot synthesis and modification of cyclic peptides through a self-cleaving on-resin protocol is described. We apply Dawson's MeDbz linker to achieve direct intramolecular peptide cyclization by thioesterification followed by S → N acyl shift. This native chemical ligation approach requires no activating additive and allows direct modification of the crude cyclic peptides in one-pot. The strategy was applied to synthesize 5 cyclic peptide natural products of varying ring size. Finally, one-pot modifications include desulfurization, fluorophore conjugation, and intramolecular disulfide formation.
Constrained Derivatives of Stylostatin 1. 1. Synthesis and Biological Evaluation as Potential Anticancer Agents
Forns, Pilar,Piró, Jordi,Cuevas, Carmen,García, Mònica,Rubiralta, Mario,Giralt, Ernest,Diez, Anna
, p. 5825 - 5833 (2007/10/03)
Hydroxyaminolactams have been used as constrained surrogates of the Ser-Leu dipeptide in the synthesis of analogues of the cycloheptapeptide stylostatin 1 (2). The rate of cyclization through formation of the Ile-Pro amide bond allowed us to prove that th
Solid phase synthesis of cyclic peptides by oxidative cyclative cleavage of an aryl hydrazide linker - Synthesis of stylostatin 1
Rosenbaum, Claudia,Waldmann, Herbert
, p. 5677 - 5680 (2007/10/03)
The synthesis of cyclic peptides using an oxidation labile aryl hydrazide linker is reported. After oxidation with NBS release from the resin is triggered via an intramolecular cyclative cleavage which proceeds without racemization.
A backbone linker for BOC-based peptide synthesis and on-resin cyclization: Synthesis of stylostatin 1
Bourne, Gregory T.,Meutermans, Wim D. F.,Alewood, Paul F.,McGeary, Ross P.,Scanlon, Martin,Watson, Andrew A.,Smythe, Mark L.
, p. 3095 - 3101 (2007/10/03)
We have developed a new 4-alkoxybenzyl-derived linker that anchors the C-terminal amino acid to the resin through the α-nitrogen atom. The linker allows BOC solid-phase peptide assembly and peptide cleavage using standard HF protocols. This linking strategy provides a versatile on-resin route to cyclic peptides and avoids the diketopiperazine formation that is prominent when using FMOC chemistry on backbone linkers. The linker was prepared by forming the aryl ether from 4-hydroxybenzaldehyde and bromovaleric acid. Subsequent reductive amination of the aldehyde with an allyl-protected amino acid ester and acylation of the resulting secondary amine provided the tertiary amide. After linking the amide to the resin, standard BOC SPPS, followed by allyl deprotection, cyclization, and HF cleavage gave cyclic peptides in high purity. To exemplify the strategy, the cytotoxic heptapeptide, stylostatin 1, was synthesized from two linear precursors. For comparison purposes, the yields of the on-resin and solution-phase cyclization were determined and found to be dependent upon the linear precursor. This linker technology provides new solid-phase avenues in accessing libraries of cyclic peptides.
