How a Peptide Synthesizer Works & How We Save You Time & Money
Despite the diversity in types, the Excedr lease program is able to source all instrument types and can accommodate any brand preferences your end-user might have. Request an estimate today and see how leasing can affect your automated peptide synthesizer’s price.
All equipment brands/models are available
The Advantages of Excedr’s Peptide Synthesizer Leasing Program:
- Eliminates the upfront cost of purchasing equipment by spreading its cost over time
- Minimizes equipment downtime with included complete repair coverage and preventive maintenance
- Takes advantage of potentially 100% tax deductible* payments, providing you significant cash-savings
- Expedites the administrative work needed for instrument procurement and logistics
- Conserves working capital, enabling you to reinvest in your core business and operations (staffing, inventory, marketing/sales, etc.)
- Accommodates all manufacturer and model preferences
*Please consult your tax advisor to determine the full tax implications of leasing equipment.
Solid-phase peptide synthesis (SPPS) has enabled the creation of synthetic peptides, which has revolutionized organic chemistry and significantly benefited biomedical research.
It was pioneered by Bruce Merrifield throughout the late 1950s and early 1960s. His technique presented a simple method for the chemical synthesis of peptides and proteins, accomplished by synthesizing peptides opposite of how we synthesize peptides in our body.
In our body, ribosomes build proteins by beginning at the amino-terminal (N-terminus) and ending at the carboxyl-terminal (C-terminus). However, using Merrifield’s technique, the opposite occurs (C-to-N).
Using his method, researchers could now assemble a peptide chain through successive reactions of amino acid derivatives on various insoluble and permeable supports, typically made of multiple resins such as polystyrene. Since SPPS’s introduction, peptide research has grown exponentially.
Moreover, SPPS led to the development of automated peptide synthesizers. These machines drastically simplified and expedited the production of both small peptides and large proteins, a task that was once aggravatingly tedious. Suddenly, preparing multiple peptide samples at once was much easier and faster.
Despite the technique’s success, several peptide researchers remained quite critical after its introduction and adoption. These critiques focused on its application to larger and larger molecules. Researchers felt that a technique that prevented the full characterization of synthetic intermediates could not give rise to authentic peptide products.
Nonetheless, Merrifield—and several other laboratories—continued to develop the method and eventually quieted the objections by improving solid-phase peptide synthesis as a technique. In research today, the definition and input of the synthesis strategy and the amino acid sequence are all that is required to perform synthesis.
Peptide synthesis has invigorated the development of different application areas where synthetic peptides are now used, including the study of protein functions, the identification and characterization of proteins, and the development of epitope-specific antibodies against pathogenic proteins. This technique also offers a range of uses in the medical and research fields, including acting as chemical messengers, inter and intra-cellular mediators, hormones, and much more.
Its processes, benefits, and costs are important considerations when looking to procure a laboratory automated peptide synthesizer.
Synthesizer Process, Benefits, & Cost
These systems allow researchers, medical professionals, and many others to create the specific proteins and peptides they need with tremendous ease. In general, there are several parts to synthesizing peptides, including resin swelling, peptide deprotection, amino acid coupling, and peptide cleavage.
Swelling the Resin
The different resins used during SPPS provide different functions. One of the most popular is polystyrene, which dissolves in hydrophobic solvents and precipitates in protic solvents (hydrogen atom bound to an oxygen atom). This resin typically contains 1% or 2% divinylbenzene (DVB) as a cross-linking agent. Cross-linked polystyrenes are insoluble in all common solvents.
However, even cross-linked polystyrene resins that are insoluble in organic solvents can be solvated and swollen by aprotic solvents such as toluene and dimethylformamide (DMF), and dichloromethane (DCM). Swelling the resin is essential in solid-phase synthesis since reaction kinetics is diffusion controlled.
Consequently, a resin that swells more will have a higher diffusion rate of reagents into the core of the matrix, resulting in shorter reaction times and more complete chemical conversions.
In general, to swell the resin, you must first accurately weigh the resin into the reaction vessel. Next, you must add an approximate amount of DMF. Afterward, you let the mixture stand at room temperature for 10 minutes or so; that way, the resin beads can swell. Lastly, you drain the DMF.
Peptide deprotection is a secondary process in synthesizing peptides where a target nucleophile and a target electrophile are isolated to promote reaction specificity. Amino acids contain a variety of reactive groups. When creating the proper peptide chain without adverse side reactions, chemical groups that block specific reactive groups are necessary. This is called blocking or protecting.
Deprotecting is the process of removing the protecting groups just after coupling to allow the other amino acids to bind, properly growing the peptide chain.
Because synthesis typically occurs by coupling the carboxyl group of the incoming amino acid to the N-terminus of the growing peptide chain (C-to-N), there are specific protecting groups for both C-termini and N-termini.
Two of the most commonly used protecting groups for the N-terminus include tert-butoxycarbonyl (Boc) and 9-fluorenylmethoxycarbonyl (Fmoc). Each group has distinct characteristics that determine its use. For example, Boc requires a strong acid such as trifluoracetic acid (TFA) to be removed from the newly added amino acid. At the same time, Fmoc is a base-labile protecting group that can be removed with a mild base like piperidine.
For C-termini, the protecting group used depends on the type of peptide synthesis used. Solid-phase peptide synthesis does not require a protecting group because the solid support acts as the protecting group.
It is important to note that virtually all processes of synthesis require the use of multiple protecting groups. Amino acid side chains represent a broad range of functional groups. They are, therefore, an area where considerable side chain reactivity occurs during peptide synthesis. For this reason, many different protecting groups are required. However, the various groups used are usually based on the benzyl (Bzl) or tert-butyl (tBu) group.
Furthermore, having groups that are entirely compatible and do not interfere with one another’s functions is essential to building the peptide chain correctly.
Amino Acid Coupling
Amino acid coupling requires the activation of carboxylic acid on the amino acid added to the reaction by using peptide coupling reagents, such as HBTU. In other words, these peptide coupling reagents are used to form the amide bonds that link separate amino acids into peptides and proteins.
This allows the N-terminus of the growing peptide chain to connect with the C-terminal of the amino acid so that the peptide bond can form and the chain can continually grow. Next, the N-terminus of the newly created peptide chain is deprived, and peptide deprotection is repeated until the entire length of the peptide is completed.
After coupling and deprotection cycles are completed, the remaining protecting groups have to be removed from the peptide that is being formed.
Cleaving out these groups is accomplished by acidolysis. The specific chemical used to remove the groups is entirely dependent on the protection groups used. For example, strong acids such as hydrogen fluoride (HF), hydrogen bromide (HBr), or trifluoromethane sulfonic acid (TFMSA) are used to cleave Boc groups. In contrast, a relatively milder acid such as TFA is used to cleave Fmoc groups.
When peptide cleavage is correctly performed, the N-terminal and C-terminal protecting groups of the last amino acid are both removed, as is any side-chain protecting groups. As is the case with deprotection, there are scavengers included during this step to react with free protecting groups.
Protein Synthesis Strategies
While peptide synthesis can be relatively chemically complex, a synthesizer makes the process much simpler. Two main methods are used to generate peptides and proteins, so it is vital to know the difference if you are looking to lease:
- Liquid Phase: This is the classic methodology that scientists implemented when they first discovered that they could generate peptides in vitro. While this solution-phase method is not as standard today, it is still used quite often when performing large-scale synthesis. Unfortunately, the difficulty and length of time needed to use this method have made it less popular since the advent of SPPS.
- Solid Phase: Solid-phase, or SPPS, is the more common method used to create peptides presently. The main reason for the success of this method is due to peptide synthesizers, the easy automation, and the high throughput that they offer. This is in line with many other biological manufacturing processes and is a massive boon to scientific and medical professionals working in molecular biology and biotechnology.
Crude peptides can be purified using various chromatography techniques. This includes high-performance liquid chromatography (HPLC), size-exclusion chromatography, ion-exchange chromatography (IEC), partition chromatography, flash chromatography, and gel permeation chromatography.
The most widely used and most powerful method for peptide purification is a mode of HPLC known as reversed-phase liquid chromatography (RPC, or RP-HPLC). It is highly versatile and employs a non-polar stationary phase alongside a polar, aqueous mobile phase made up of water and, in some cases, a water-miscible organic solvent that acts as a modifier.
For purification, RPC separates the target peptides from impurities left over from the synthesis steps, such as isomers and peptide products from side reactions with free coupling and protecting groups, among other impurities, through the use of columns packed with spherical particles during the stationary phase.
Customized Protein Synthesizer Leases to Fit Every Need
Thanks to developments in biotechnology and bioengineering, the interest in peptide synthesis has increased, and researchers in the life sciences are using peptide synthesis and chemistry to further their work involving the study of protein molecules and their functions. This also includes antibody production, antibiotic drug development, vaccine production and design, and cancer diagnosis and treatment.
If you’re interested in leasing a peptide synthesizer, or any another instrument used in protein research, such as a microarray scanner, let us know. We can help you procure the equipment you need to get the job done.
Fill out our contact form or give us a call at (510) 982-6552 and we can discuss your specific needs in-depth.
This off-balance sheet financing structure provides three options at the end of the term. The lessee has the option to return the equipment to the lessor, renew at a discounted rate, or purchase the instrument for the fair market value. Monthly payments are also 100% tax deductible which yields additional monetary savings.
If you recently bought equipment, Excedr can offer you cash for your device and convert your purchase into a long-term rental. This is called a sale-leaseback. If you’ve paid for equipment within the last ninety days, we can help you recoup your investment and allow you to make low monthly payments. This also frees up money in your budget rather than tying it down to a fixed asset.
Peptide Synthesis Device Manufacturers & Models
Liberty PRIME, CarboMAX, Liberty Blue HT12, Flex-Add Liberty Blue, Liberty Life, Discovery Bio, Razor Cleavage System, Automatic Microwave Peptide Synthesizer, Manual Peptide Synthesis
Initiator+ Alstra, Microwave Assisted Organic Synthesis (MAOS), Initiator+ SP Wave, Syro, Syro II, Syros XP, S2PS, Syro Heating Block, S1PS, Alstra Remote, Initiator Peptide Workstation
Gyros Protein Technologies:
Prelude X, Symphony X, Tribute, Symphony/Quartet, Sonata/Sonata ST, PS3, PurePrep Pathway, Ultra PurePep Pathway
CS136 Series, CS136S, CS136X, CS336 Series, CS336S CS336X, CS536 Series, CS536, CS536X, CS936 Series, CS936S, CS936, CS936X, Commercial Scale Peptide Synthesizers, Research Scale Peptide Synthesizers, Pilot Scale Peptide Synthesizers
Eclipse, Infinity 2400, Focus series, Focus Xi, Focus XC, Focus XC II, Focus XC III, Apex 396, Apex 396 Parallel Synthesizer, APEX 396HT, Apex 396HT Peptide Library Synthesizer, Model 400, Model 400-P4, Titan 357, Endeavor 90, Endevor 90-III, Matrix 384, Labmate, SMART Synthesis Software, Microwave Peptide Synthesizer, Peptide Research Instrument, Peptide Personal Synthesizer, Peptide Production Synthesizer, Parallel Synthesizer, Automated Multiple Peptide Synthesizer, Peptide Library Synthesizer, Pilot Production Place Synthesizer, Automated Split-and-Combine Combination Peptide Synthesizer, Personal Manual Parallel Synthesizer
MultiPep RSi, MultiPep CF, ResPep SLi, Slide Spotting Robot, CelluSpots, SPOT module
Activo-P11 Automated Peptide Synthesizer, ActivoPep, Activo-P14 Peptide Synthesizer, Activo-P12 Cleavage Device, Activo-LS55 Automated Peptide Synthesizer, Activo-S44 Automated
PPSQ-51A/53A, Isocratic System, Gradient System
Tetras Peptide Synthesizer
Peptide Machines, Inc.: