Shelton Pernille Tofteng, Jensen Knud J
IGM, Faculty of Life Sciences, University of Copenhagen, Zealand Pharma, Glostrup, Denmark.
Methods Mol Biol. 2013;1047:131-9. doi: 10.1007/978-1-62703-544-6_9.
In the backbone amide linker (BAL) strategy, the peptide is anchored not at the C-terminus but through a backbone amide, which leaves the C-terminal available for various modifications. This is thus a very general strategy for the introduction of C-terminal modifications. The BAL strategy was originally developed using a trisalkoxybenzyl linker, but since then range linkers (handles) with different properties have also been developed. The BAL anchoring is established by anchoring an aromatic aldehyde, typically a trisalkoxybenzaldehyde, to the solid support, followed by attachment of the first amino acid residue by reductive amination. This can be used as a general approach for the introduction of other C-terminal modifications as well as functionalities, such as fluorophors. The second step is an acylation of a secondary amine, followed by standard Fmoc-based solid-phase synthesis to assemble the final peptide. One useful application of this strategy is in the synthesis of C-terminal peptide aldehydes. The C-terminal aldehyde is masked as an acetal during synthesis and then conveniently demasked in the final cleavage step to generate the free aldehyde. Another application is in the synthesis of peptide thioesters with a C-terminal glycine.
在主链酰胺连接子（BAL）策略中，肽不是锚定在C端，而是通过主链酰胺进行锚定，这使得C端可用于各种修饰。因此，这是一种引入C端修饰的非常通用的策略。BAL策略最初是使用三烷氧基苄基连接子开发的，但从那时起，也开发了具有不同性质的一系列连接子（手柄）。BAL锚定是通过将芳香醛（通常是三烷氧基苯甲醛）锚定到固相载体上，然后通过还原胺化连接第一个氨基酸残基来实现的。这也可以用作引入其他C端修饰以及功能基团（如荧光团）的通用方法。第二步是仲胺的酰化反应，然后进行基于Fmoc的标准固相合成以组装最终的肽。该策略的一个有用应用是合成C端肽醛。C端醛在合成过程中被掩蔽为缩醛，然后在最终裂解步骤中方便地脱掩蔽以生成游离醛。另一个应用是合成具有C端甘氨酸的肽硫酯。
