Peptide-Pilot

 

Peptide-Pilot - continuous-flow-solid-phase-peptide-synthesizer

Configuration Overview

The Peptide-Pilot is a unique peptide synthesizer designed to reduce the drug development cycle time by reducing the time required to produce significant quantities of a target peptide.  Synthesis times are reduced from weeks to less than a day when compared with the normal room temperature batch methods.  Crude purity is excellent even when unnatural amino acids are required.

Peptide-Pilot variable bed flow reactor unloading

Systems available to order now for delivery in 2024

Peptide-Pilot systems can be ordered now with the installations scheduled from Q3 2024.

The first Peptide-Pilot was commissioned at the research site of a major pharmaceutical company in December 2023.   A further batch of 3 Peptide-Pilot systems is under construction, two of these systems are available for order and can be configured to suit your exact needs.

Please contact Vapourtec today to discuss how the Peptide-Pilot can fit into the workflow towards your new peptide therapeutics.

Peptide-Pilot reactor cylinder and plunger

Synthesis scale 2.0 mmol to 30.0 mmol

The peptide pilot is supplied with three sizes of resin cartridges providing a broad range of synthesis scale from 2 mmol to 30 mmol of crude peptide.

For a typical GLP-1 based therapeutic peptide this represents between 8 grams and 120 grams of crude peptide.

Using the unique Peptide-Pilot, 120 grams of crude 30-mer peptide can be synthesized in under 1 day including the automated addition of side-chains.

Peptide-Pilot crude purity GLP-1 15mmol

Highest quality crude peptides at large scale

The Peptide-Pilot uses Vapourtec’s proprietary single-pass continuous flow method utilising the variable bed flow reactor (VBFR) technology.

This method of peptide synthesis ensures crude peptide is produced having high crude purity.

In addition, this method of peptide synthesis can be scaled predictably from laboratory scale at 0.1 mmol (using Vapourtec’s Peptide-Explorer) to 30 mmol on the Peptide-Pilot without further development.

VBFR-unload-Peptide-Pilot_

Uses Vapourtec’s patented reactor technology (VBFR) for continuous flow single pass SPPS

In 2017 Vapourtec’s developed and patented a new reactor technology for peptide synthesis.  This reactor has been named the variable bed flow reactor (VBFR).

The key benefit of this reactor is it maintains the resin at a constant packing density during the entire synthesis.  As the resin increases and decreases in volume during the synthesis, the packaging density is maintained ensuring optimum interaction between reagents and solvents and the peptidyl resin.  Channeling is eliminated and the reactor volume is minimised.

Another significant benefit of the VBFR technology is the real time measure of reactor volume.  This data delivers completely new data regarding the peptide synthesis, providing new insights into peptide aggregation.   The precise timing and magnitude of each aggregation event can be monitored and quantified in real time.

Using this data, the adoption of pseudoproline dipeptides or other aggregation mitigation options can be considered with new scientific rigour.

 

Peptide-Pilot loading reagents

Heated reactors (VBFR) ensures fast cycle times even at largest scale

Vapourtec’s patented variable bed flow reactor (VBFR) technology has precise temperature control.

The ability to optionally run the synthesis at temperatures between 40°C and 90°C provides short cycle times even at large scale.  Maintaining the resin at elevated temperature also, improves resin solvation, reduces reagent consumption, and ensures 100% completion of difficult couplings and coupling of unnatural (non-canonical) amino acids.

Reaction temperatures can be changed rapidly allowing the optimum temperature to be selected for each amino acid.  For example, residues prone to racemisation can be activated and coupled under ideal conditions.  The Peptide-Pilot’s state of the art software automatically selects the optimum reactor temperatures for each of the natural amino acids.

Peptide-Pilot VBFR reactor unload

Typical reaction time for a 30-mer peptide at 30 mmol scale is 15 hours

The adoption of single pass continuous flow using the VBFR for SPPS allows synthesis times that are less affected by scale.

A 30-mer peptide at 30 mmol scale will only take 15 hours using the Peptide-Pilot.  Using traditional batch reactors this same peptide will take between 2 and 3 weeks to synthesise at 30 mmol scale.

If the Peptide-Pilot is used, each iteration of a target peptide can save more than 2 weeks.  The time and cost saving not to mention the potential saving of patent life on a new drug development programme can be highly significant.

Peptide-Pilot loading DMF tanks

Minimises solvent and reagent usage

Solvent usage is typically less than 70 ml per mmol / cycle even when using PEG resins.

Typical syntheses use between 3 and 5 equivalents of amino acids, however the single-pass continuous flow allows expensive unnatural amino acids to be used as the limiting reagent if this is desired.

By way of example, a 30-mer peptide can be synthesised at 30 mmol scale using less than 65 litres of solvent.

The Peptide-Pilot has capacity for 120 litres of wash solvent and features automated switching between solvent containers.

The whole system has been designed to ensure fully automated synthesis from start to finish including the automated addition of sidechains.

fmoc peptide synthesis

Fmoc solid phase peptide chemistry with DIC and oxyma activation

The robustness of Fmoc/tBu solid-phase peptide synthesis has been taken to new levels by the adoption of single-pass continuous flow combined with Vapourtec VBFR technology.

Peptide-Pilot peptide synthesis real time inline data

Continuous in-line analytics including resin solvation data and UV absorption data

A significant benefit of the VBFR technology is the real time measure of reactor volume.  This delivers completely new data regarding the peptide synthesis, providing new insights into peptide aggregation.   The precise timing and magnitude of each aggregation event can be monitored and quantified in real time.

Using this data, the adoption of pseudoproline dipeptides or other aggregation mitigation options can be considered with new and increased scientific rigour.

In addition to the resin solvation data, single pass continuous flow facilitates precise quantification of Fmoc deprotection from the resin.  The state-of-the-art Peptide-Pilot software calculates and plots the area under the curve (AUC) for each deprotection and presents this in real time.

Peptide-Scaleup reactor loading

A synthesis optimised on the Peptide-Explorer can be transferred to the Peptide-Pilot without further development

The highly reproducible and predictable scale-up of continuous flow reaction protocols means reactions from Vapourtec’s lab scale systems can be easy scaled to the Peptide-Pilot.

0.1 mmol scale reactions optimised using the Peptide-Explorer can be scaled 300 fold to 30 mmol reactions on the Peptide-Pilot without further development.

 

 

Contact us for a Peptide-Pilot synthesizer quotation

 

 

 

 

 

 

 

 

Get in touch

For more information on flow chemistry systems and services please use the contact methods below.

Call us on +44 (0)1284 728659 or Email us