1. Solid phase chemical ligation employing a rink amide linker for the synthesis of histone H2B protein
Muhammad Jbara, Mallikanti Seenaiah, Ashraf Brik Chem Commun (Camb). 2014 Oct 25;50(83):12534-7. doi: 10.1039/c4cc06499b.
Presented here is a solid phase chemical ligation strategy employing native chemical ligation and the commercially available Rink-amide linker as a key element in our approach. The method was applied for the synthesis of histone H2B, which sets the ground for the rapid preparation of posttranslationally modified analogues of this protein.
2. C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation
Panagiotis Stathopoulos, Serafim Papas, Vassilios Tsikaris J Pept Sci. 2006 Mar;12(3):227-32. doi: 10.1002/psc.706.
Decomposition of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture.
3. A convenient approach to synthesizing peptide C-terminal N-alkyl amides
Wei-Jie Fang, Tatyana Yakovleva, Jane V Aldrich Biopolymers. 2011;96(6):715-22. doi: 10.1002/bip.21600. Epub 2011 Feb 9.
Peptide C-terminal N-alkyl amides have gained more attention over the past decade due to their biological properties, including improved pharmacokinetic and pharmacodynamic profiles. However, the synthesis of this type of peptide on solid phase by current available methods can be challenging. Here we report a convenient method to synthesize peptide C-terminal N-alkyl amides using the well-known Fukuyama N-alkylation reaction on a standard resin commonly used for the synthesis of peptide C-terminal primary amides, the peptide amide linker-polyethylene glycol-polystyrene (PAL-PEG-PS) resin. The alkylation and oNBS deprotection were conducted under basic conditions and were therefore compatible with this acid labile resin. The alkylation reaction was very efficient on this resin with a number of different alkyl iodides or bromides, and the synthesis of model enkephalin N-alkyl amide analogs using this method gave consistently high yields and purities, demonstrating the applicability of this methodology. The synthesis of N-alkyl amides was more difficult on a Rink amide resin, especially the coupling of the first amino acid to the N-alkyl amine, resulting in lower yields for loading the first amino acid onto the resin. This method can be widely applied in the synthesis of peptide N-alkyl amides.
