Peptides and protein serve vital purposes in the biochemistry, research, and medical worlds. As such, their production has become an equally essential service. Production of these compounds is made possible by Solid-phase peptide synthesis (SPPS). Some of the synthetic peptides of import as pharmaceutical or commercial products include sugar-substitute aspartame.
As of 2008, the peptide therapeutics industry crossed the multi-billion-dollar mark, with over 400 peptides currently used in clinical studies. Therefore, efficient, sustainable, and rapid techniques for chemical synthesis are of the utmost concern. Some peptides have to undergo further processing to make them suitable for their intended use even after their production. These modifications now exist in varying types according to the intended use of peptides.
This article brings you five examples of these peptide modifications and the purposes they serve.
What is Peptide Modification?
Peptide modification includes methods that allow the chemoselective alteration of amino acids and peptides to render them better resembling the native protein or peptide fragment they were modeled after. As a powerful technique, peptide modification enables the introduction of elements that promote the later application of peptides.
At the commercial level, peptide modification services are sourced to Peptide Synthesis companies that specialize in meeting the research needs of different organizations and research institutions. This is because modifications aren’t only performed post-synthetically but also during the peptide creation phase by the use of properly derived amino acids.
Among the peptide modification are the following:
- N-Methylation of the peptide backbone
- Fluorescent labeling
- MAP peptides
- Cage peptides
Among this long list, let’s look at the five most common.
Several natural peptides that engage in vital biological activities exist in cyclical forms. Cyclization is useful during peptide synthesis to conform a peptide to the desired format, mainly is modeled on the section of a more considerable protein or peptide. The cyclic modification takes several techniques such as the following:
In all these instances, cyclization is usually carried out following the synthesis of the linear peptide. Of these three cases, sidechain-to-sidechain is the most common and involves bridging cysteine residues with disulfide.
Usually, suppose a synthetic peptide is produced to mimic a larger peptide or protein section. In that case, the peptide lacks the active conformation of the parent protein to which it should correspond. With the introduction of hydrocarbon bridges, also called staples, in-between residues, you can enable the peptide to take on an alpha-helical structure. Comparing stapled peptides to their non-stapled counterparts, it’s easy to see that they have much better activity. Also, they have the added advantage of improved cell penetration and more resistance to enzymatic hydrolysis.
N-Methylation of The Peptide Backbone
Natural peptides undergo N-Methylation, and when introduced to the synthetic peptide, this interferes with normal hydrogen bonding. Also, it produces a peptide with better resistance to elimination and biodegradation. The synthesis of the N-methylated backbone in the peptide is accomplished by integrating the respective N-methylated amino acid derivatives. But there exists an alternative approach that entails a Mitusnobu reaction with N-(2-nitrobenzenesulfonyl) and other reagents. This relatively new technique was used to prepare a library of cyclic peptides with N-methylated amino acids.
Phosphorylated peptides assume a regulatory role with the majority of protein kinases. Phosphorylation happens to threonine, tyrosine, and serine residues. Phosphoserine, phosphotyrosine, and phosphothreonine derivatives can be integrated with peptides in the synthesis phase or incorporated post-synthesis. Meanwhile, phosphoramidite reagents are favored for introducing phosphate groups after manufacturing the peptide.
However, selective phosphorylation is attainable by using selectively displaceable protecting groups on the serine, tyrosine, or threonine residues to be phosphorylated.
Like teicoplanin and vancomycin, glycopeptides are vital antibodies instrumental in treating bacterial infections capable of withstanding other antibodies. The use of other glycopeptides is due to their ability to induce the immune system. Studies involving such peptides produce a more enhanced treatment of infections since several microbial antigens are glycosylated. Also, glycopeptides could become vital in cancer research and studies on the immune resistance to tumors because cancer cells show irregular glycosylation of cellular membrane proteins. The method used in the production of glycopeptides is Fmoc/tBu protocols.
It’s better to add the cost of peptide modification when you request a quote online for peptide synthesis, mainly as it’s essential for the intended use of your peptides. Most peptide synthesis companies will provide you with a list of their clients’ modification services. Therefore, you need to ensure the one you require is listed before paying for services. And if you don’t find what you’re looking for, it’s always advisable to talk to company personnel. Lastly, it’s crucial to ascertain that all synthesized and modified peptides undergo stringent quality control procedures to ensure the utmost purity and quality.