Welcome to the Biotage Peptide Synthesis Blogs.

      What is solid phase peptide synthesis?

      Sep 25, 2019 9:47:21 PM / by Elizabeth Denton posted in Biotage, Developments, synthesis, peptide, peptide synthesis, solid phase peptide synthesis, cleavage, synthesis tips, orthogonal protecting groups, synthesis optimization, method development, FMOC, BOC

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      More and more groups are exploring the utility of peptides with an ever widening variety of applications. And although peptides are getting cheaper to purchase outright, many groups are continuing to bring peptide synthesis in house. As more groups join the peptide community, I frequently encounter questions about the basics of peptide synthesis.

      In today's post, I'd like to cover a little history of solid phase synthesis as well as highlight some differences between the chemistries.

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      How to choose the right resin functionality for solid phase peptide synthesis

      Jun 11, 2019 8:30:01 PM / by Elizabeth Denton posted in Peptides, solid phase peptide synthesis, synthesis tips, synthesis optimization

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      As a chemist new to the peptide community, there are many choices that have to be made.  Which coupling reagents to use? Heat or no heat to promote chemistry? And most importantly, which resin?  I have talked previously about resin choices, from loading levels to swelling capacity and how they affect the synthesis outcome.  But I haven't addressed yet a fundamental feature of commercially available resins, and that's the functional handle to which the peptide chain is conjugated.

      In today's post, I'll describe some, and I mean only some, of the most commonly used chemical functionalities for Fmoc-based solid phase peptide synthesis and some scenarios in which you would choose one resin type over another.

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      Using double coupling to improve your peptide synthesis

      Apr 29, 2019 6:06:48 PM / by Elizabeth Denton posted in peptide workflow, solid phase peptide synthesis, synthesis tips

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      There are several strategies employed when a peptide synthesis requires optimization.  Typically, the first thing considered is whether or not to double couple specific amino acids within the sequence.  This is somewhat of a change in mentality from traditional room temperature synthesis strategies where double coupling is frequently used for the entire peptide sequence.

      In a previous post, I briefly described several scenarios in which doubling coupling can be used in conjunction with microwave heating to improve the overall crude peptide purity.  In today’s post, I will delve more deeply into the question of whether or not double coupling is necessary to improve your peptide synthesis.

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      Optimizing the removal of an ivDde protecting group

      Apr 29, 2019 6:05:57 PM / by Elizabeth Denton posted in peptide workflow, solid phase peptide synthesis, synthesis tips

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      As the complexity of peptides continues to grow, so does the use of amino acids with side chain protecting groups that can be selectively removed, leaving the peptide on resin and the remaining side chain protecting groups intact.  While there are  protocols to be found in the literature, they may not work to the highest level of efficiency every single time.  This can lead to disasterous results for any subsequent chemistry.

      In today’s post, I’ll evaluate a variety of conditions for removing an ivDde protecting group from the lysine side chain amine.

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      How To Load The First Amino Acid Onto Wang Resin

      Apr 29, 2019 6:05:23 PM / by Elizabeth Denton posted in peptide workflow, solid phase peptide synthesis, first amino acid loading, resin loading, synthesis tips

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      While resins loaded with the natural 20 amino acids are commercially available these days, there may be times when loading the first amino acid onto the resin in house may be necessary.  And unlike loading the first amino acid onto amide-leaving resins, the first coupling reaction for C-terminal acids can be chemically more challenging.

      There are several protocols published both in the literature as well as in technical notes from many peptide reagent and instrument suppliers, but they typically occur at room temperature over extended periods of time (3-24 hours and repeated).  In today’s post, I’ll evaluate several conditions suitable for efficiently loading the first amino acid onto Wang-type resin.

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      How to quantify your first amino acid loading onto Wang resins

      Apr 29, 2019 6:04:33 PM / by Elizabeth Denton posted in solid phase peptide synthesis, quantifying resin loading, first amino acid loading, resin loading, synthesis tips

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      While many of the standard amino acids can be purchased pre-loaded onto Wang type resins, there are still cases where coupling the first amino acid onto Wang resin manually is necessary.  In my case, an unnatural amino acid was required on the C-terminus so there was not a commercially available source.
      This coupling reaction comes with it’s own set of challenges, which is why many people perform a large scale batch preparation of the pre-loaded resin.  But that’s for a later discussion.  In today’s post I’ll address a different question. How do you quantify the amount of amino acid loaded onto the resin?

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      How long are amino acid stock solution stable for successful solid phase peptide synthesis?

      Apr 29, 2019 6:03:52 PM / by Elizabeth Denton posted in peptide, peptide workflow, solid phase peptide synthesis, synthesis tips

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      In today’s post I’ll answer the above question by comparing the crude purity of peptides synthesized using amino acid stock solutions or freshly dissolved amino acids.

      In previous posts I have described using high concentrations of amino acids to improve your peptide synthesis among some other tips and tricks.  But there is a particularly handy tip that was left off the list.

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