77284-61-8Relevant academic research and scientific papers
Synthesis and comparative properties of two amide-generating resin linkers for use in solid phase peptide synthesis
Deng, Fang-Kun,Mandal, Kalyaneswar,Luisier, Sam,Kent, Stephen B.H.
body text, p. 545 - 550 (2011/11/14)
Well-characterized resins of high purity are critical for effective solid phase peptide synthesis (SPPS). The quality of commercial (4-methyl)benzhydrylamine-resin (MBHA-resin), used for the synthesis of peptide amides, is not consistent and residual ketone functionalities are frequently present. Such ketone or aldehyde impurities lead to the formation of acylation-resistant deletion peptides in SPPS. To avoid these undesirable side reactions, we have optimized the preparation of two amide-generating linkers, which, in combination with aminomethyl-resin prepared directly from polystyrene resin, serve as alternatives to MBHA-resin for peptide amide synthesis. Then we have explored their comparative properties in SPPS. Use of sonication in reductive amination facilitated the synthesis of both benzhydrylamine (BHA) and MBHA linkers. We have optimized the preparation of two amide-generating linkers for use in stepwise solid phase peptide synthesis. In combination with aminomethyl-resin prepared directly from polystyrene resin, these linkers serve as alternatives to MBHA-resin for peptide amide synthesis. Copyright
Benzhydrylamine linker grafting: A strategy for the improved synthesis of C-terminal peptide amides
Alewood, Dianne,Hopping, Gene,Brust, Andreas,Reid, Robert C.,Alewood, Paul F.
experimental part, p. 551 - 557 (2011/11/12)
The standard p-MBHA resin used during Boc-chemistry synthesis of peptides carrying C-terminal carboxamides is compromised by batch-to-batch variations in its performance. This can cause artificially 'difficult' couplings during peptide chain assembly, which may ultimately lead to failed syntheses given the inability to achieve acceptable coupling yields. To overcome these problems, we have developed a new approach by grafting a functionalized benzhydrylamine linker onto well-characterized and well-performing PAM resins. We combine optimized Boc-chemistry, high-performing PAM resins and new benzhydrylamine-based linkers to achieve improved syntheses of peptide amides. Here we present the synthesis of two new benzhydrylamine linkers and their attachment to selected PAM resins. This novel solid support was evaluated through the synthesis of selected 'difficult' conotoxins and monitoring the coupling efficiency using quantitative ninhydrin assay. The results show a superior performance of the novel linker solid support compared to the standard p-MBHA resins routinely used. In summary, we describe an alternative linker-resin system that allows improved access to C-terminal amide peptides employing Boc/Bzl chemistry. Benzhydrylamine enzhydrylamine linkers (a/b) were grafted onto high-performing Phe-PAM resins for Boc solid phase peptide amide synthesis. Fast couplings with high fidelity were achieved enabling the synthesis of selected conotoxins that previously demonstrated artificially 'difficult sequences' on commercially available p-MBHA resins. Copyright
