The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Rapid Flow‐Based Peptide Synthesis
Open accessAbstract
A flow‐based solid‐phase peptide synthesis methodology that enables the incorporation of an amino acid residue every 1.8 min under automatic control or every 3 min under manual control is described. This is accomplished by passing a stream of reagent through a heat exchanger into a low volume, low backpressure reaction vessel, and through a UV detector. These features enable continuous delivery of heated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentration of reagents in the reaction vessel, quickly exchanging reagents, and eliminating the need to rapidly heat reagents after they have been added to the vessel. The UV detector enables continuous monitoring of the process. To demonstrate the broad applicability and reliability of this method, it was employed in the total synthesis of a small protein, as well as dozens of peptides. The quality of the material obtained with this method is comparable to that for traditional batch methods, and, in all cases, the desired material was readily purifiable by RP‐HPLC. The application of this method to the synthesis of the 113‐residue Bacillus amyloliquefaciens RNase and the 130‐residue DARPin pE59 is described in the accompanying manuscript.
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Cites
Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
Merrifield, R. B. (1963) · Journal of the American Chemical Society · doi:10.1021/ja00897a025 · Cited by 7,825
Synthesis of Proteins by Native Chemical Ligation
Dawson, P. E., Muir, T. W., Clark‐Lewis, I., & Kent, S. B. H. (1994) · Science · doi:10.1126/science.7973629 · Cited by 4,190
Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids
Fields, G., & NOBLE, R. L. (1990) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1990.tb00939.x · Cited by 2,490
In situ neutralization in Boc‐chemistry solid phase peptide synthesis
Schnölzer, M., Alewood, P. F., Jones, A., Alewood, D., & Kent, S. B. H. (1992) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1992.tb00291.x · Cited by 1,055
Protein Chemical Synthesis by Ligation of Peptide Hydrazides
Fang, G., Li, Y., Shen, F., Huang, Y., Li, J., Lin, Y., Cui, H., & Liu, L. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201100996 · Cited by 812
Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences
Coin, I., Beyermann, M., & Bienert, M. (2007) · Nature Protocols · doi:10.1038/nprot.2007.454 · Cited by 638
CHEMICAL SYNTHESIS OF PEPTIDES AND PROTEINS
Kent, S. B. H. (1988) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.57.070188.004521 · Cited by 508
Methods and Protocols of Modern Solid Phase Peptide Synthesis
Amblard, M., Fehrentz, J., Martínez, J., et al. (2006) · Molecular Biotechnology · doi:10.1385/mb:33:3:239 · Cited by 498
Microwave heating in solid-phase peptide synthesis
Pedersen, S. L., Tofteng, A. P., Malik, L., & Jensen, K. J. (2011) · Chemical Society Reviews · doi:10.1039/c1cs15214a · Cited by 333
Self-citationPentelute, B., Gates, Z. P., Tereshko, V., Dashnau, J. L., Vanderkooi, J., Kossiakoff, A., & Kent, S. (2008) · Journal of the American Chemical Society · doi:10.1021/ja8013538 · Cited by 222
Self-citationKakaç, S., Liu, H., & Pramuanjaroenkij, A. (2002) · CRC Press eBooks · doi:10.1201/9781420053746 · Cited by 222
Automated Chemical Synthesis of a Protein Growth Factor for Hemopoietic Cells, Interleukin-3
Clark‐Lewis, I., Aebersold, R., Ziltener, H., et al. (1986) · Science · doi:10.1126/science.3079915 · Cited by 216
High-Efficiency Solid Phase Peptide Synthesis (HE-SPPS)
Collins, J. M., Porter, K. A., Singh, S. K., & Vanier, G. S. (2014) · Organic Letters · doi:10.1021/ol4036825 · Cited by 195
Dryland, A., & Sheppard, R. C. (1986) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/p19860000125 · Cited by 192
Kimmerlin, T., & Seebàch, D. (2005) · Journal of Peptide Research · doi:10.1111/j.1399-3011.2005.00214.x · Cited by 191
Protein Chemical Synthesis by Ligation of Peptide Hydrazides
Fang, G., Li, Y., Shen, F., Huang, Y., Li, J., Lin, Y., Cui, H., & Liu, L. (2011) · Angewandte Chemie · doi:10.1002/ange.201100996 · Cited by 144
Some ‘difficult sequences’ made easy
Hyde, C. B., Johnson, T., OWEN, D., et al. (1994) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1994.tb00541.x · Cited by 135
Hyde, C. B., Johnson, T., Owen, D., et al. (1994) · PubMed · Cited by 124
Accelerated chemical synthesis of peptides and small proteins
Miranda, L. P., & Alewood, P. F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1181 · Cited by 111
[2] Rapid in situ neutralization protocols for Boc and Fmoc solid-phase chemistries
Alewood, P. F., Alewood, D., Miranda, L. P., Love, S. G., Meutermans, W. D. F., & Wilson, D. T. R. (1997) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(97)89041-6 · Cited by 93
Solid-phase peptide synthesis under continuous-flow conditions.
Lukas, T. J., Prystowsky, M. B., & Erickson, B. W. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.5.2791 · Cited by 67
VARANDA, L. M., & de Miranda, M. T. M. (1997) · Journal of Peptide Research · doi:10.1111/j.1399-3011.1997.tb01175.x · Cited by 62
Quibell, M., Turnell, W. G., & Johnson, T. (1994) · The Journal of Organic Chemistry · doi:10.1021/jo00086a025 · Cited by 56
Aussedat, B., Fasching, B., Johnston, E., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja2111459 · Cited by 54
Rapid solid-phase synthesis of a calmodulin-binding peptide using controlled microwave irradiation
Bacsa, B., & Kappe, C. O. (2007) · Nature Protocols · doi:10.1038/nprot.2007.300 · Cited by 50
Racemization in stepwise solid-phase peptide synthesis at elevated temperatures
Souza, M. P., Tavares, M. F. M., & de Miranda, M. T. M. (2004) · Tetrahedron · doi:10.1016/j.tet.2004.03.070 · Cited by 50
A new support for polypeptide synthesis in columns
Bayer, E., Jung, G., Halász, I., & Sebestian, I. (1970) · Tetrahedron Letters · doi:10.1016/s0040-4039(01)83961-7 · Cited by 42
Scott, R. P. W., Chan, K. K., Kučera, P., et al. (1971) · Journal of Chromatographic Science · doi:10.1093/chromsci/9.10.577 · Cited by 38
Tofteng, A. P., Pedersen, S. L., Stærk, D., & Jensen, K. J. (2012) · Chemistry - A European Journal · doi:10.1002/chem.201200711 · Cited by 20
Self-citationHan, Y., 平木, 治., & Barany, G. (1997) · PubMed · doi:10.1021/jo9622744
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- 2000, Fmoc Solid‐Phase Peptide Synthesis: A Practical Approach, Vol. 222
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The greening of peptide synthesis
Lawrenson, S. B., Arav, R., & North, M. (2017) · Green Chemistry · doi:10.1039/c7gc00247e · Cited by 205
Varró, N., Mándityné Huszka, B., Erdei, E., Mándoki, A., & Mándity, I. M. (2025) · Chemistry–Methods · doi:10.1002/cmtd.202500010 · Cited by 8
Metadata
- Authors
- Simon, M. D., Heider, P. L., Adamo, A., Vinogradov, A. A., Mong, S. K., Li, X., Berger, T., Policarpo, R. L., Zhang, C., Zou, Y., Liao, X., Spokoyny, A. M., Jensen, K. F., & Pentelute, B. L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Corresponding author
- Pentelute, Bradley L.
- ORCID
- Venue
- ChemBioChem
- Publisher
- Wiley
- Published
- 2014-03-11
- Volume
- 15
- Issue
- 5
- Pages
- 713-720
- ISSN
- 1439-4227 (ISSN-L)
- 1439-7633
- PMC
- PMC4045704
- OpenAlex
- W1508435089
- Cited by
- 4
- References
- 30
- Citations by year
- 2024: 1 · 2021: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ChemBioChem (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PMC
- Funders
- National Institute of General Medical Sciences (T32GM008334, F32GM101762)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Innovative Microfluidic and Catalytic Techniques Innovation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- solid-phase peptide synthesis, heat exchangers, UV monitoring, reagent delivery, peptide purification
- MeSH terms
- Amino Acid Sequence, Equipment Design, Molecular Sequence Data, Peptides, Time Factors, Solid-Phase Synthesis Techniques
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