Peptide Synthesis Applications

The use of specially modified amino acids is available for a wide variety of peptide synthesis applications. These modified monomers are frequently extremely expensive and their implementation is limited by these costs.

The application of heat represents a useful tool to optimize the production of challenging synthetic peptides, and a new technology, induction heating, has been introduced on the Prelude X.

Poster presented at EPS2018

Poster presented at EPS2018

Automated solid phase peptide synthesis (SPPS) increases reliability, efficiency, and crude purity for peptides and peptoids.

Peptides are studied because of their range of biological activities in the body. As receptorbinding molecules, peptides have been investigated for therapeutic uses. Unfortunately, in the body peptides are easily broken down by proteases (enzymes that digest proteins and peptides) and have difficulty crossing cell membranes.

Many naturally occurring peptides contain intradisulfide bridges, which play an important role in biological activities.

YIYGSFK is a substrate for the protein tyrosine kinase. Tyrosine kinase activity is increased in several human tumors, so the study of its substrates may lead to a greater understanding of cancer. In this application, a tyrosine kinase substrate was synthesized and modified with a biotinylated lysine and a racemic amino acid thioester on a Prelude peptide synthesizer using Boc chemistry.

The IntelliSynth™ UV-monitoring and Feedback Control System is a powerful tool that can be used to determine difficult cycles during a synthesis on the Tribute™ peptide synthesizer. It works by monitoring the extent of Fmoc removal during the deprotection reaction by measuring the concentration of removed Fmoc in the deprotection solution at 301 nm.

In peptide synthesis and peptide library synthesis, piperidine is a common reagent for Fmoc removal. However, piperidine is a controlled substance, which requires special handling.

Very fast synthesis times are achievable using optimized Fmoc conditions. Traditional peptide chemistry typically resorts to using extended reaction times to maintain synthesis yields, often resulting in deprotection times of 20-30 minutes and coupling times of an hour or more. It is accepted that speed is gained at the expense of purity.

Cyclic peptides have interesting biological properties. They are increasingly being used as drug targets as they often are more metabolically stable and have greater affinity and selectivity to biological receptors than their linear counterparts.

In peptide synthesis, piperidine is a common agent for Fmoc removal. However, piperidine is a controlled substance which requires special handling and cannot be used in some countries. Therefore, it would be useful to identify alternative deprotection reagents to piperidine for Fmoc removal.

The peptide hormone ?-melanocyte stimulating hormone, or ?-MSH, stimulates melanogenesis and plays a role in appetite, energy balance, and sexual function (1).

Cyclic peptides have interesting biological properties. They are increasingly being used as drug targets as they often are more metabolically stable and have greater affinity and selectivity to biological receptors than their linear counterparts.

PTI has just developed No-Foam beads for large-scale syntheses on the Symphony® and PreludeTM.

The copper-catalyzed azide-alkyne cyclization (CuAAC), the most commonly recognized variant of “click chemistry,” has emerged as a powerful technique for ligation, conjugation, and cyclization reactions of peptides.

Peptide nucleic acid (PNA) is a DNA mimic in which the deoxyribose phosphate backbone is replaced with a neutral pseudopeptide backbone composed of 2-aminoethyl glycine linkages. The four natural nucleobases (adenine, guanine, cytosine and thymine) are retained as side chains.

Biotinylation is the process of covalently binding biotin to a protein or other molecule. Due to the specificity and high binding affinity of biotin to the proteins avidin and streptavidin, biotinylation is commonly used in immunoanalytical techniques such as ELISA, ELISPOT and western blots.

Cyclization is known to improve the stability, potency, and selectivity of many peptides. One method for peptide cyclization which has generated tremendous interest is the use of olefin metathesis to create “stapled” peptides.

Download the application note and learn more about how oxopiperazine helix mimics (OHMs) have been successfully prepared using a fully automated method on Prelude X. Application of this method to the synthesis of diversified libraries will accelerate discovery of novel ligands for protein targets.

Heat-assisted synthesis has been shown to reduce the time necessary to produce high-purity linear peptides, and its application to the synthesis of cyclic peptides may provide similar advantages.

Building upon the strength of the original Prelude platform, the Prelude X adds heating, oscillation shaking, and UV monitoring to deliver uncompromised speed, yield, reagent savings, and flexibility, creating the most complete peptide synthesis solution available.

Peptides have been recognized as highly selective and generally well tolerated drug candidates, increasing the demand for rapid access to different peptide sequences in order to accelerate the evaluation of potential therapeutics.

The coupling reagent COMU has been demonstrated to be highly efficient in the synthesis of a variety of peptides.

New and optimized methods for rapid peptide synthesis, combined with instruments capable of parallel synthesis enable the production of peptide libraries with high throughput.

The Symphony X™ multiple peptide synthesizer offers the most flexibility and independent protocols of any instrument on the market, making it an ideal platform for high-throughput process development.

Type-II diabetes, caused by chronic insulin resistance and a progressive decline in pancreatic ?-cell function, affects over 150 million people worldwide [1]. The 37-mer human islet amyloid polypeptide (IAPP) (Figure 1) or amylin, is a major contributor to the amyloid deposits found in the pancreases of patients with typeII diabetes [2,3].

Human ?-amyloid (1-42) (Figure 1) is a major component of the plaque deposits found in the brains of patients with Alzheimer’s disease (AD) [1]. b-amyloid is in constant demand for the continued research into the pathology, diagnostic tools, and potential therapeutics for AD.

Human parathyroid hormone (1-84) (PTH) (Figure 1) is produced by the parathyroid glands and regulates calcium and phosphate metabolism. PTH acts on PTHR1 receptors to stimulate bone formation and is used as a treatment for osteoporosis and hypoparathyroidism, a rare deficiency of parathyroid hormone [1,2]

Peptide based drug discovery and research is increasingly at the forefront in addressing new therapeutic challenges due to their high target selectivity and potency with low toxicity. Automated solid phase peptide synthesis (SPPS) increases reliability, efficiency and crude purity for peptides in drug discovery and development.

Poster presented at EPS2018