Grants and Contracts Details
Description
There have been many fascinating advances in peptide coupling and green solvent methods in
recent years.[1-4] In order to achieve successful translation of this research to industry, more
innovation is required in flow chemistry.[3-7] One promising technology which can achieve lower
solvent use and be scaled up industrially is membrane enhanced liquid phase peptide
synthesis.[6, 8] Two common issues noted in liquid phase synthesis, is peptide and solvent
recovery. Peptide recovery can be improved by increasing the size of the growing peptide by
using star structures and implementing multiple membrane filtration stages. [8-11] To keep
building on this research momentum, this proposal first intends to extend star size to larger
systems such as 6-arm and 8-arm species. Secondly, a secondary membrane nanofiltration
system will be developed and optimized to recycle solvent back into the reactor. The overall goal
is to increase reaction sustainability by decreasing fresh solvent use via recycling and increasing
peptide yield via star size modification.
References:
1. Al Musaimi, O., B.G. de la Torre, and F. Albericio, Greening Fmoc/tBu solid-phase peptide synthesis. Green
Chemistry, 2020. 22(4): p. 996-1018.
2. Behrendt, R., P. White, and J. Offer, Advances in Fmoc solid-phase peptide synthesis. J Pept Sci, 2016.
22(1): p. 4-27.
3. Bogdan, A.R. and A.W. Dombrowski, Emerging Trends in Flow Chemistry and Applications to the
Pharmaceutical Industry. J Med Chem, 2019. 62(14): p. 6422-6468.
4. Gordon, C.P., The renascence of continuous-flow peptide synthesis - an abridged account of solid and
solution-based approaches. Org Biomol Chem, 2018. 16(2): p. 180-196.
5. Farkas, V., et al., Cost-Effective Flow Peptide Synthesis: Metamorphosis of HPLC. Organic Process Research
& Development, 2021. 25(2): p. 182-191.
6. Peeva, L., et al., Continuous purification of active pharmaceutical ingredients using multistage organic
solvent nanofiltration membrane cascade. Chemical Engineering Science, 2014. 116: p. 183-194.
7. Weeranoppanant, N. and A. Adamo, In-Line Purification: A Key Component to Facilitate Drug Synthesis
and Process Development in Medicinal Chemistry. ACS Med Chem Lett, 2020. 11(1): p. 9-15.
8. So, S., et al., Membrane enhanced peptide synthesis. Chem Commun (Camb), 2010. 46(16): p. 2808-10.
9. Castro, V., et al., Novel Globular Polymeric Supports for Membrane-Enhanced Peptide Synthesis.
Macromolecules, 2017. 50(4): p. 1626-1634.
10. Li, H., et al., Resin-free peptide synthesis mediated by tri(4-benzoylphenyl) phosphate (TBP) derivatives as
small-molecule supports. Organic Chemistry Frontiers, 2020. 7(4): p. 689-696.
11. Yeo, J., et al., Liquid Phase Peptide Synthesis via One-Pot Nanostar Sieving (PEPSTAR). Angew Chem Int Ed
Engl, 2021. 60(14): p. 7786-7795.
Status | Finished |
---|---|
Effective start/end date | 10/1/21 → 1/31/23 |
Funding
- American Chemical Society: $50,000.00
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