When it comes to solid-phase peptide synthesis, there are plenty of compounds you can use. You can easily get confused by the number of options and start wondering which one is the right resin. Chemists know that different resins deliver different synthesis outcomes. 

Today, we will take a closer look at resins and analyze their functionality for solid-phase peptide synthesis. If you are a chemist yourself, the information will help choose the right resin for your purposes. 

The information will be of great use to those looking for peptide synthesis services, as you will learn to check whether they use the right resin for your solid-phase peptide synthesis needs or not.

What Is The Purpose of Solid-Phase Peptides?

If we could choose the most critical thing to consider when choosing the right resin functionality, then it is the following question – “What is the purpose of a solid-phase peptide?” 

The answer to this question will help you choose just the right resin functionality. The resin functionality in a specific use case scenario is determined by the type of C-terminal linkers, which can be either acid, amide, or other. 

Resins With C-Terminal Acid Linkers

Resins with C-terminal acid linkers are a prevalent option in solid-phase peptide synthesis. It is used for acid substrates. However, it can be hard to work with them in terms of successfully cleaving peptides from the resin. The most commonly used C-terminal acid linker is Wang. 

Many companies choose to invest in Wang resin preloaded with the first amino acid, though. Loading the first amino acid by yourself is an arduous and risky task. You have to use concentrated TFA to liberate the side chain protecting groups and resin at the same time. If you fail, instead of cleaving the peptide from the resin, you can cause side-chain racemization. 

Resins With C-Terminal Amide Linkers

The most popularly used resin among the C-terminal amide linker resins is the Rink Amide. Unlike acid resins, which are very channeling to work with, amide resins are easy to handle. Why? The first amino acid loading is a simple amide bond. TFA is used here as well as it enables you to cleave the peptide from the resin. But instead of using high-concentrations, a 1% TFA solution can efficiently cleave it. To be safely stored, these resins have to be protected by a Fmoc group. To render the free amine and use them, you will have to pretreat them with piperidine.

Another C-terminal amide resin is Sieber resin. Its use case is rather particular. It is used for peptides that contain sterically bulky amino acids. Sieber resin packs some acidic resistance, and it can be used in mildly acidic conditions.

Resins With C-Terminal Other Linkers

This category encompasses resins able to facilitate workflows in the native chemical ligation chemistry. Over the years, the process of solid-phase peptide synthesis became more complex. Resins in this category have a role in addressing the new challenges.

One of the examples is the group of safety-catch resins. Their purpose is to enable the formation of a C-terminal peptide thioester. These peptides were discovered by Kenner and expanded by Ellman. Other resins in this category are N-acylureas and hydrazides. 

Pairing the resin type with your needs is just one side of the problem. Every resin reacts in different conditions, and choosing the right resin for your industrial purposes can be a tough thing to do. If you are less experienced in this field, you can seek help from professional peptide synthesis service.

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Emma G

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