The blog discusses about the common linkers for solid phase.
In solid phase synthesis, the group that links the substrate or the substance being modified to the resin bead is a very important component of the process. The linker is a special protecting group that ties up a functional group which re-emerges at the end of the process. Linkers that have this inherent ability to facilitate attachment and breakdown in quantitative yield are considered to be the most effective.
Carboxylic Acid Linkers
The first linking group that was used during synthesis of peptides is called Merrifield resin. It is cross-linked polystyrene that is functionalized with a chloromethyl group. The carbonyl group is linked with a cesium carboxylate salt by a nucleophilic displacement of chloride in DMF. Hydrogen fluoride is used as a reagent in the process of regeneration of carboxylic acid. Wang Linker is the second class of linkers used for carboxylic acids. The linker is typically attached to cross-linked polystyrene, polyacrylamide, and TentaGel to form Wang resin. The resin was designed for the synthesis of peptide making use of the Fmoc protection strategy, and due to the activated design of benzyl alcohol, the carboxylic acid product can be cleaved with TFA.Carboxamide Linkers
The Wang ester linkage can be broken down with ammonia in order to produce primary carboxamide ; however, it is a complex reaction. Treatment with ammonia for a prolonged period of time could result in racemisation of a certain type of peptides. To create carboxmide in mild acidic conditions, chemists have developed a linking group. Methylbenzhydrylamine or MBHA linker was the first linker developed on polystyrene for enhanced peptide synthesis using Boc protection strategy. A new linker was developed by Sieber having greater acid lability using a xanthenyl derivate. The acid-labile 9-xanthenyl group has been used to offer superior protection to the amide group of glutamine and asparagine. Since the xanthenyl group is less acid liable compared to Boc, an extra –OCH2 group was added to improve acid liability between polystyrene and the anchor.Alcohol Linkers
Ellmann and Thompson developed a hydroxyl linker based on the tetrahydropyranyl or THP protecting group. Diverse range of alcohols add readily to dihydropyran and the THP protecting group that is stable to strong base, however, it can easily be cleaved with acid. The linker is linked to Merrifield resin. The trityl group serves as a good acid labile protecting group for a number of heteroatoms. It has been used to anchor alcohols in the synthesis of β-mercaptoketones.Watson International Ltd. is one of the leading chemical trading companies offering an extensive range of chemical products for a diverse range of industries. If you are looking for high quality chemicals at affordable prices, you can contact watson-int.com.
