Towards sustainable, racemization-free Wang resin esterification via mediated bromination
(2024) KBKM05 20241Pure and Applied Biochemistry
Computational Chemistry
- Abstract
- Owing to a forecasted 53% increase in therapeutic peptide requirement until 2026 – corresponding to almost 23 tonnes of product – a high pressure will be put on the peptide manufacturing industry. Not only because of the increased demand, but also due to the important role of solvents in peptide synthesis. The peptide business will face challenges as stricter regulations from chemical authorities oppose the use of many universal solvents and listing them as substances of very high concern (SVHC). Albeit there have been previous research reporting the success of exchanging traditionally used dichloromethane (DCM) and N,N-dimethylformamide (DMF) – as they are unsustainable both due to negative effects on the environment and suspected as... (More)
- Owing to a forecasted 53% increase in therapeutic peptide requirement until 2026 – corresponding to almost 23 tonnes of product – a high pressure will be put on the peptide manufacturing industry. Not only because of the increased demand, but also due to the important role of solvents in peptide synthesis. The peptide business will face challenges as stricter regulations from chemical authorities oppose the use of many universal solvents and listing them as substances of very high concern (SVHC). Albeit there have been previous research reporting the success of exchanging traditionally used dichloromethane (DCM) and N,N-dimethylformamide (DMF) – as they are unsustainable both due to negative effects on the environment and suspected as carcinogenic and reprotoxic respectively – many processes in peptide production still engages them. This could be a result of the greener protocols failing in showing results of the same yield or low amount of racemization formation, as the less sustainable alternatives. Therefore, there is a significant demand for development of new methods using green solvents and surpassing the results of classic procedures. In this thesis, a novel approach aiming to move towards sustainable peptide synthesis through bromination and esterification of Wang resin is proposed. Through mild bromination conditions, a combination of green solvents was found to be successful in performing as solvent mixture both for bromination of Wang resin, and in esterification of protected isoleucine (Ile) amino acid (AA) to the loaded Wang. (Less)
- Popular Abstract
- For the past 100 years, peptide synthesis has been crucial for the development of new medicines. Today in a modern time, the shift to focus on incorporating green solvents could be the next step in the peptide synthesis evolution. Still, many people in the industry have a traditional mindset believing the switch for green alternatives in the reactions would sacrifice efficiency for sustainability. However, there are green solvents proving that we can have both.
With the aim to develop sustainable methods for peptide manufacturing, a novel approach with a new combination of green solvents is presented to be used superior to the unsustainable and traditionally used dichloromethane (DCM) and N,N-dimethylformamide (DMF). Replacing DCM and DMF... (More) - For the past 100 years, peptide synthesis has been crucial for the development of new medicines. Today in a modern time, the shift to focus on incorporating green solvents could be the next step in the peptide synthesis evolution. Still, many people in the industry have a traditional mindset believing the switch for green alternatives in the reactions would sacrifice efficiency for sustainability. However, there are green solvents proving that we can have both.
With the aim to develop sustainable methods for peptide manufacturing, a novel approach with a new combination of green solvents is presented to be used superior to the unsustainable and traditionally used dichloromethane (DCM) and N,N-dimethylformamide (DMF). Replacing DCM and DMF for the new green solvent mixture would not only propose a solution to the environmental issue, but it would also benefit the people on the production line. Indeed, the traditional solvents have gotten attention due to the health threat they carry for those handling them. As DCM is a suspected carcinogenic and DMF holds risk for damaging fertility, there is certainly a big need for an alternative solvent now when peptide manufacturing is on the rise and the demand is expected to continuously grow in the years to come. The combination of solvents that this study suggests is undoubtedly more sustainable and safer to handle.
Beside successful results in reactions for coupling of amino acids, the green combination also offers the possibility of usage during enhancement of the solid support that helps in the peptide synthesis. The improved solid support both increases stability and the reaction rate, making it advantageous for peptide synthesis reactions. Therefore, a protocol for improving the solid support in mild conditions in the green solvent has also been developed. The benefits posed by using the same solvent for both the enhancement of the support and for the following synthesis could be many – significantly the opportunity to limit excess solvent use while keeping the same sustainable solvent for a major part of the synthesis. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9165260
- author
- Hermansson, Matilda LU
- supervisor
- organization
- course
- KBKM05 20241
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- applied biochemistry, green solvents, peptide synthesis, Wang resin
- language
- English
- id
- 9165260
- date added to LUP
- 2024-11-05 09:55:41
- date last changed
- 2024-11-05 09:55:41
@misc{9165260,
abstract = {{Owing to a forecasted 53% increase in therapeutic peptide requirement until 2026 – corresponding to almost 23 tonnes of product – a high pressure will be put on the peptide manufacturing industry. Not only because of the increased demand, but also due to the important role of solvents in peptide synthesis. The peptide business will face challenges as stricter regulations from chemical authorities oppose the use of many universal solvents and listing them as substances of very high concern (SVHC). Albeit there have been previous research reporting the success of exchanging traditionally used dichloromethane (DCM) and N,N-dimethylformamide (DMF) – as they are unsustainable both due to negative effects on the environment and suspected as carcinogenic and reprotoxic respectively – many processes in peptide production still engages them. This could be a result of the greener protocols failing in showing results of the same yield or low amount of racemization formation, as the less sustainable alternatives. Therefore, there is a significant demand for development of new methods using green solvents and surpassing the results of classic procedures. In this thesis, a novel approach aiming to move towards sustainable peptide synthesis through bromination and esterification of Wang resin is proposed. Through mild bromination conditions, a combination of green solvents was found to be successful in performing as solvent mixture both for bromination of Wang resin, and in esterification of protected isoleucine (Ile) amino acid (AA) to the loaded Wang.}},
author = {{Hermansson, Matilda}},
language = {{eng}},
note = {{Student Paper}},
title = {{Towards sustainable, racemization-free Wang resin esterification via mediated bromination}},
year = {{2024}},
}