Custom Peptide Synthesis for a Variety of Applications

Custom Peptide Synthesis for a Variety of Applications

The accessibility of custom peptide synthesis services and technologies opens up expansive opportunities in all aspects of industry and scientific research. Never ending combinations of peptides can be custom designed and used in a whole host of applications. The conjugation of a peptide to a protein, a peptide modification or the production of a peptidomimetic may improve the pharmacokinetics of a therapeutic in development while the labeling of a peptide with a fluorophore or stable isotope may enhance protein quantification in diagnostic assays.

Customizing Your Peptide with Biosynth

Having numerous peptide experts spread across global production sites, Biosynth have the experience and capability to manufacture a large selection of custom peptides to a multikilogram scale. From producing single or simple peptides, to a variety of complex labelled products and extensive libraries for screening, our custom made peptides can be used in protein characterization, proteomics tools, epitope mapping and even in clinical trials.

While the site at Kentucky is certified to ISO 9001:2015, our Dutch site, according to EudraLex, volume 4, part II, can manufacture GMP peptide drug substances for use in clinical trials. Other examples of our chemistries we can offer customers as part of our custom peptide synthesis services are: solid phase peptide synthesis, solution phase synthesis, native chemical ligation, glycochemistry, small molecule synthesis, high throughput synthesis, PEGylations, and more.

What are the benefits of Peptide-Protein Conjugates?

Often small peptide molecules used in therapeutic and diagnostic applications exhibit a narrow therapeutic index, due to having a short half-life and showing non-specific binding. However, through conjugation to a protein or peptide pharmacokinetics can be significantly improved. These peptide-protein conjugates tend to have an increased half-life and a greater specific distribution to the target site.

Due to long half-life properties, and its ability of being taken up endocytically by tumour cells, the Albumin protein is an excellent candidate to be a carrier for tumour imaging and diagnosis. It is also used in the imaging of Rheumatoid arthritis as it has been shown to accumulate at sites of inflammation. Therefore conjugating drugs and imaging probes to the protein Albumin is an attractive application for peptide-protein conjugates in the therapeutic and diagnostic industry.

Stimulating antibodies for immunization, is another beneficial application of peptide-protein conjugates and an examples of what our team of scientists can offer. Further examples of customized conjugations available are: conjugation to proteins such as Ovalbumin and Ferritin and the conjugation of Cys-containing peptides to chosen proteins using selective heterobifunctional crosslinkers.

Peptide Modifications

Peptide modifications are significant tools in the field of research and facilitate studies into protein interactions and complexes. When incorporated into peptides these modifications stabilize peptide and protein complexes. In the pharmaceutical and therapeutics industry they are also assets to diagnosis, drug delivery and treatments. Specifically, linkers and spacers are used to link fluorophores to peptides in diagnostic assays, the penetration of cell membranes by peptides is enhanced through C-terminal modifications such as N-alkyl amides and unnatural amino acids play a key role in antibody drug conjugates.

If you require the enhancement or increased specificity of your protein’s function, you should consider Biosynth’s custom peptide modification service. We can modify your peptide in any way you like from: acylation and amidation, biotynylation, cyclizations, alkylation, lipidation, pegylation, phosphorylation, coupling of bifunctional chelating agents and prosthetic groups for imaging agents and to click chemistry. Read more about these peptide modifications on our website.

Overcoming the Challenge of Multi-Disulfide and Cyclic Peptide Synthesis

The synthesis of peptides through folding, while simultaneously maintaining their biological activity has opened up a challenge to the scientific world. Biosynth have demonstrated their expertise in this area using either the natural folding method or the orthogonal protection strategy to fold complex molecules.

Multi-disulfide peptides are such ‘hard to fold’ molecules, and can be synthesized through the two strategies stated above. Examples of multi-disulfide peptides which have high therapeutic potential include native molecules and analogs of conotoxins, defensins, hepcidins, chemokines and ion channel blockers (ShK, HwTX4, charybdotoxin, iberiotoxin, margatoxin, ProTx-II, mu-conotoxins, etc).

Compared to their corresponding linear peptides, cyclic peptides have improved biological activity, have greater conformational rigidity and their cyclic structure protects them from exopeptidase hydrolysis. Overall their performance as therapeutic molecules is refined with improved binding and selectivity of target. From Biosynth you can request cyclizations and peptide macrocycles such as Head to Tail, Internal Lactam, and stapled peptides.

What are Peptidomimetics?

Peptidomimetics are synthetic peptides, designed to mimic the structure and biological function of natural peptides. The use of these peptidomimetics is paramount in medicinal chemistry as they help to increase the stability and selectivity, which was lacking from their natural counterpart. As a result, they play a major role in drug discovery.

The Biosynth custom synthesis repertoire includes the design of peptidomimetics such as Chloromethylyketones, Depsipeptides and the following:

• Hydroxyethylene Isostere:?Is a nonhydrolyzable mimetic, which can be used in medicinal chemistry in the replacement of scissile peptide bonds.
• Aldehydes:?In a recent study, (Wenhao Dai et al. 2022), peptidomimetic aldehydes were shown to inhibit enzyme activity in Enterovirus and SARS-CoV-2 while also demonstrating good pharmacokinetic properties. Thus making aldehyde petidomimetcs an interesting tool for future drug development against these viruses.
• Phosphonates:?Phosphonates contain a phosphanate (P(O)(OH)2) group which is attached through a P-C bond. As non-hydrolyzable phosphate mimics, phosphates can serve as inhibitors of enzymes. There are many phosphate -based drugs with different therapeutic applications such as bisphosphonates can be used to treat osteoporosis while besifovir is an antiviral.

Peptide Labelling

Using a mini-PEGTM spacer, Biosynth can incorporate labels into your custom peptide, such as: TAMRA, which can be used to label nucleotides and study the sequencing of amino acids, the fluorescence labelling reagent, FITC or Biotin. Biotin tags can be useful in: protein research, ELISA’s, western blots, immunohistochemistry, flow cytometry and many more assays and diagnostic applications. Additionally we can introduce incorporate Rhodamine, special or d-amino acids, stable isotopes, EDANS, Dabsyl, Dansyl, Abz, thiolactic acids, and other molecules of your choice into your peptide. Read on to find out more about our stable isotope custom synthesis.

Stable Isotope Labelled Peptides and Services

Within the clinical diagnostic industry, quantitative protein analysis methods such as antibody based assays (ELISA) and Liquid chromatography–mass spectrometry (LC-MS) have been critical in discovering and measuring levels of biomarkers prevalent in disease states. Developments in mass spectrometry methods have made them advantageous in terms of having increased reliability and sensitivity. Furthermore, as LC-MS methods can be multiplexed, several assays to quantify a protein is not needed and instead only one single assay. These methods use a mass-shifted, stable-isotope-labeled peptide calibrators.

When atoms (N, C, H) in natural amino acids are substituted with their ‘heavy isotope’ variant, a stable isotope labelled peptide is formed. Usually these substitutions are 12C by 13C (carbon-13), 14N by 15N (nitrogen-15), and 1H by 2H (deuterium). As the chemical reactivity and physiochemical properties of stable isotope labeled peptides and their corresponding non-labelled peptides are the same stable isotope peptides are perfect for Absolute QUAntitation (AQUA) applications.

Stable-isotope-labeled peptide calibrators are spiked into samples, and the ratio of labelled and unlabelled peak heights determines the quantification. Currently this methods, known as the stable isotope dilution methods (SID) is the gold-standard in multiple reaction monitoring (MRM) and selective reaction monitoring (SRM).

As leaders in isotope labelled peptides since 2001 and the pioneers of the first complete collection of peptide and antibody SIS products and services, Neptune?, our team at Biosynth can give you expert advice and support in designing your peptide for use in proteomics. Below are examples of our stable isotope labelled peptides and services:

TrypTides? Custom Heavy Labelled Peptide Synthesis

In addition to our TrypTidesTM catalog products, we offer TrypTides? Custom Heavy Labeled Peptide Synthesis, which are optimized for mass spectrometry performance and available in a 96 peptide library format.

TrypRaws?

We can synthesize amino acids and resins isotopically labelled with Arg (+10) and Lys (+8). In addition, we have SISCAPA? assay technology stable isotope standards for SISCAPA workflows.

Anti-peptide Antibodies Against Tryptic Peptide Fragments

Biosynth have developed a TrypBodies? platform, for anti-peptide antibodies against tryptic peptide fragments. These platforms have positive field applications in that they can provide higher level analytical performances of MS in biomarker research or proteomics. We have also created specialized protocols to optimize polyclonal and monoclonal antibodies for use in iMRM.

High Throughput Custom Peptide Synthesis

Having a high-throughput production facility means that Biosynth can deal with large peptide orders and deliver them to our customers reliably, rapidly and flexibly. We also take pride in the high quality of our state of the art, custom peptides and that is why each peptide undergoes meticulous quality control (QC) methods such as: LC/MS, MALDI-MS and HPLC. Read our brochures to learn more about the key features of our high-throughput custom peptide synthesis and find out more about our custom peptide synthesis services on our website.