We use cookies to enhance your experience. By continuing to browse this website, you agree to our use of cookies. More information.

In this interview, CEM Corporation and News-Medical Life Sciences are talking about using their product Liberty Blue for modification and automated and efficient solid-phase peptide synthesis of drug-related peptides.

CEM Corporation is the world's leading supplier of microwave instruments for analytical and synthetic chemistry applications. Recently, we have been committed to synthesizing modified and drug-related peptides using an instrument called Liberty Blue™ Automatic Microwave Peptide Synthesizer.

The instrument can be used for a variety of synthetic applications, including peptide cyclization, peptidomimetic synthesis, and peptide modification.

Let me start with RCM and hydrocarbon binding, which is a form of cyclization that connects the side chains of two amino acid building blocks. Stapling can stabilize the alpha helix and has been shown to increase protease resistance and cell permeability.

Disulfide bond is an oxidative bond formation that occurs in many biologically active peptides, the most common being venoms and therapeutic agents. Disulfide bonds can stabilize the secondary structure and, similar to binding, can increase protease resistance and target affinity. These bridges can be formed synthetically.

You can also form bonds between thiols to create peptides with multiple disulfide bonds. It is also possible to carry out head-to-tail cyclization and side chain side chain condensation.

Liberty Blue can also be used for peptidomimetic synthesis, especially peptidomimetic and peptidomimetic-peptide hybrid synthesis.

Peptoids are polymers with multiple N-substituted glycines. Since their amide bonds are completely replaced, they are resistant to proteolytic degradation. This makes them attractive targets for drug development.

In addition, due to the lack of amide hydrogen, the secondary structure of the peptidomimetic has changed. The incorporation of peptidomimetic monomers is not as simple as chain extension with Fmoc and substituted glycine derivatives. Instead, a two-step acetylation-the nucleophilic replacement method-is necessary.

First, bromoacetic acid is coupled to the end of the peptide or peptidomimetic monomer. Then, a primary amine is added to replace the bromide ion, providing a terminally substituted glycine residue. At this point, the peptidomimetic is ready to extend the channel further without removing Fmoc.

Although this two-step procedure is not as simple as the one-step merging process, it provides a lot of flexibility. There are thousands of commercially available methods available for peptide-like synthesis, opening up many opportunities for chemical discovery.

In addition to peptide-like synthesis, another peptide mimicry application of Liberty Blue is the incorporation of PNA monomers.

N-terminal acetylation is a wide-ranging modification naturally found in eukaryotes and prokaryotes, thereby changing the charge and hydrophobicity of the peptide, affecting its folding characteristics and target affinity. N-terminal acetylation can also increase protease resistance. Automatic N-terminal acetylation is fast and simple.

Incorporation of non-standard hindered amino acids, such as quaternary ammonium centers containing Aib or nitrogen-substituted N-methylalanine, is another important process that can be performed. Combining these types of derivatives is becoming more and more popular. AIB induces alpha helix formation, and like peptidomimetic monomers, N-methylalanine increases protease resistance and alters secondary structure.

Combining these building blocks is simple. The addition of one of these hindered amino acids requires a standard single coupling. If two hindered amino acids are connected to each other, the double coupling needs to be extended. Linking natural amino acids to more hindered residues requires standard double coupling.

We can also add phosphate amino acids. Phosphorylation introduces phosphate groups to the tyrosine, threonine, or serine residues of the peptide. Enzymatic phosphorylation regulates the functions of many peptides and proteins. The ability to synthesize phosphorylated peptides can be used to study peptide function and signal transduction.

This phosphorylation process has its advantages over other methods. Traditionally, the production of phosphorylated peptides requires the synthesis of unmodified linear sequences, followed by a post-synthesis phosphorylation step. This step is difficult to perform and often produces impure peptides. The introduction of Fmoc-derived monobenzyl protected phosphate amino acid significantly improved the synthesis process.

Derivatives can be easily merged using Liberty Blue and our standard coupling procedure. However, phosphoserine needs to be deprotected at room temperature because it appears to be easily dephosphorylated at high temperatures during the deprotection process. After incorporating its neighboring amino acids, we can resume using the elevated deprotection temperature.

Symmetrically branched peptides usually have very ideal physical, chemical and biological properties, mainly due to their multivalent binding capacity and improved protease resistance.

For example, if you want to synthesize a peptide with four independent chains of the same amino acid sequence, you must look back when the first branch occurred. Treatment with a deprotection solution can provide two free amines in preparation for chain extension.

This process does not require special loops or methods, and all standard single coupling methods can be used. It is also possible to go further than this level of branch.

These results are shocking because the synthesis of branched peptides by SPPS is often challenging because of the inherent close proximity of the extended peptide chains. The application of microwave energy helps overcome the challenges of spatial conflict and poor coupling efficiency.

Another application of Liberty Blue is automatic orthogonal lysine deprotection and functionalization. Functionalization of peptide side chains, such as bioconjugation, labeling, and branching, is an influential and indispensable synthetic tool. Many amino acids can be functionalized, but lysine has received special attention.

Similar to the formation of disulfide bonds between Cys residues that require orthogonal protection, lysine functionalization also requires protection of removable groups without affecting the rest of the peptide.

The three most common derivatives may be Lys (Mmt), Lys (ivDde) ​​and Lys (Alloc). Mmt is deprotected under weakly acidic conditions, Lys(Alloc) requires a palladium catalyst, and ivDde requires diluted hydrazine.

Let us consider the asymmetric peptide branch as an extension of lysine functionalization. LF Kymera peptide has two different chain extension points; one is the original peptide chain and the other is the extension of the lysine side chain. This tells you that you first need to synthesize a linear chain, then deprotect the lysine and extend it further.

Lys(ivDde) ​​is often the orthogonal derivative of choice, so you need to use the Boc-protected phenylalanine structural unit at the last position of the original chain. After capping with this Boc-protected amino acid, you can deprotect Lys(ivDde) ​​and construct a sequence that extends from this point.

Similar to the symmetric branching of peptide synthesis, you can take asymmetric branching further.

There are other peptide modifications compatible with Liberty Blue, including the incorporation of glycosyl amino acids and orthogonal glutamate for deprotection and functionalization.

For more information on any of these methods, please visit our website or send an email to [email protected].

CEM's customers come from extremely diverse industries and provide a wide range of products and services, but they have one thing in common. They need reliable and cost-effective methods for chemical testing, analysis and monitoring. This is where CEM comes in. As a pioneer in the field of microwave chemistry, we provide products that can accelerate and automate classical chemical methods and improve accuracy and repeatability.

Sponsored Content Policy: Articles and related content published by News-Medical.net may come from sources of our existing business relationships, provided that such content adds value to the core editorial spirit of News-Medical.net, that is, education and informing the website Visitors interested in medical research, science, medical devices and treatments.

Published in: Drug Discovery and Pharmaceuticals | Molecular and Structural Biology | Insights from Industry | Cell Biology | Microbiology | Life Science News | Biochemistry | Automation and Sample Preparation | Fluorescence

Tags: acetylation, amino acids, B cells, catalysts, cells, chemical analysis, eukaryotes, food, glutamic acid, glycine, helix, ion, life sciences, lysine, palladium, peptides, phenylalanine, phosphoric acid Chemicals, polymers, prokaryotes, reproduction, serine, T cells, therapeutic agents, threonine, tyrosine

Please use one of the following formats to cite this article in your paper, essay, or report:

CEM Corporation-Life Sciences. (2019, April 24). Synthesize modified and drug-related peptides. News-Medical. Retrieved from https://www.news-medical.net/news/20190424/Synthesizing-Modified-and-Pharmaceutically-Relevant-Peptides.aspx on December 13, 2021.

CEM Corporation-Life Sciences. "Synthesis of modified drug-related peptides". News-Medical. December 13, 2021. <https://www.news-medical.net/news/20190424/Synthesizing-Modified-and-Pharmaceutically-Relevant-Peptides.aspx>.

CEM Corporation-Life Sciences. "Synthesis of modified drug-related peptides". News-Medical. https://www.news-medical.net/news/20190424/Synthesizing-Modified-and-Pharmaceutically-Relevant-Peptides.aspx. (Accessed on December 13, 2021).

CEM Corporation-Life Sciences. 2019. Synthesize modified and drug-related peptides. News-Medical, accessed December 13, 2021, https://www.news-medical.net/news/20190424/Synthesizing-Modified-and-Pharmaceutically-Relevant-Peptides.aspx.

In this interview, we interviewed Dr. Georg Meisl and introduced his latest research that helped determine the cause of the progression of Alzheimer's disease.

Allen Lee, CEO of Portwell Technology, USA

In this interview, News-Medical talked with Allen Lee from Portwell Technology in the United States about their work in the company and how they became a leading supplier of medical equipment and medical imaging equipment.

Dr. Gary Heiman and Dr. Brad Kamitaki

Researchers designed a new diagnostic model to predict the response of patients with generalized epilepsy to drug treatment.

News-Medical.Net provides this medical information service in accordance with these terms and conditions. Please note that the medical information on this website is intended to support rather than replace the relationship between patients and doctors/doctors and the medical advice they may provide.

This website complies with HONcode standards to obtain reliable health information: verify here.

News-Medical.net-AZoNetwork website

Owned and operated by AZoNetwork, © 2000-2021