Welcome to the Biotage Peptide Synthesis Blogs.

      How long should I let my cleavage reaction stir at room temperature?

      Sep 27, 2019 3:30:52 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization

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      As the rules for cell permeability continue to be elucidated, peptides are increasingly being used to deliver either themselves or cargo to the cell’s interior.  One thing is clear, increasing the overall cationic charge of the peptide enhances it’s delivery to not only the cytoplasm, but also the nucleus or other subcellular compartments.  To achieve the positive charge, large numbers of arginine residues are most often incorporated into the peptide sequence.

      This begs the question though, should I change my cleavage protocol?  In today’s post, I’ll evaluate several lengths of time used to cleave and fully deprotect an Arg-rich peptide sequence.

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      Five Tips and Tricks for Success in Solid Phase Peptide Synthesis

      Sep 27, 2019 3:26:17 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Alstra

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      In my role as a peptide application scientist, I have had the pleasure of working with many groups that are venturing into the world of peptides for the first time.  Although it seems rather  straightforward to experienced synthetic chemists, producing acceptable yield and purity certainly comes with unique challenges in solid phase peptide synthesis .

      In this post I would like to present some of the tips and tricks that I have picked up along the way.

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      Post synthesis workup: What steps are necessary and what aren't?

      Jun 19, 2019 5:35:32 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Workflow, V-10

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      You’ve just finished a peptide synthesis and now it’s time to cleave the peptide from the resin. You’ve selected a specific cleavage cocktail, performed the reaction and now what? The vast majority of peptide chemists will precipitate their peptide using an ether solution, lyophilize, and move on to purification. But is that the only option?

      In today’s post I’ll highlight an alternative strategy that saves both processing time, potentially dangerous reagents, all without compromising the integrity of the recently synthesized peptide.

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      Using microwave heating to expedite your allyl ester or alloc deprotection

      Jun 11, 2019 8:28:51 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Alstra

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      Orthogonal amino acid protecting groups effectively expand the chemical tool kit available to peptide chemists allowing for synthesis of much more complex molecules.  Often times, orthogonal protecting groups are used in Fmoc-based chemistry to facilitate post-synthesis modifications of peptides, like the addition of small molecule fluorophores and more commonly now, peptide cyclization efforts.

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      Using double coupling to improve your peptide synthesis

      Apr 29, 2019 6:06:48 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Alstra

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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.

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      Optimizing the removal of an ivDde protecting group

      Apr 29, 2019 6:05:57 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis

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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.

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      How to handle peptides that contain methionine

      Mar 28, 2019 2:24:34 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Automation, Alstra

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      The diversity of amino acid side chain functionalities, coupled with secondary structure, gives peptides and proteins their unique properties and activities. However, when it comes to chemically synthesizing peptides or even small proteins, the side chain functionalities can do more harm than good.

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      What do you do when your peptide synthesis fails?

      Feb 14, 2019 2:40:48 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis

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       It never fails. A sequence looks relatively straightforward on paper and it's of moderate length so you start synthesizing without too much thought into the protocol. Your synthesis is finished and you run the analytical HPLC but your product is nowhere to be found (or only very small quantities). So what went wrong? And what can you do differently to increase your crude yield and purity?

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      Webinar: Synthesizing Disulfide-rich Peptides

      Feb 1, 2019 4:46:25 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Webinar, Alstra

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      Elizabeth Denton, PhD, Senior Scientist Peptide Chemistry, recorded a webinar titled Disulfide Rich Peptides: Optimizing and Automating Syntheses with Regioselective Formation of Disulfide Bonds. To learn more, read the description below as well as watch the recording!

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      Synthesis of peptides containing three disulfide bonds: can it be fully automated?

      Jan 4, 2019 3:56:10 PM / by Elizabeth Denton posted in Peptides, Troubleshooting and Optimization, Synthesis, Alstra

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      I have experimented a lot with disulfide rich peptides lately, finding conditions that work well for not only the linear synthesis, but also for on-resin cysteine oxidations.  Although simple scaffolds are useful for determining orthogonal protecting group removal and cysteine oxidation conditions, many of the peptides of interest today are much more complex – three or more disulfide bonds, and often head-to-tail cyclization.

      In today’s post, I put to use three orthogonal protection strategies to optimize a fully automated synthesis of linaclotide.

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