WO2018044356A1 - In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures - Google Patents

In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures Download PDF

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Publication number
WO2018044356A1
WO2018044356A1 PCT/US2017/028254 US2017028254W WO2018044356A1 WO 2018044356 A1 WO2018044356 A1 WO 2018044356A1 US 2017028254 W US2017028254 W US 2017028254W WO 2018044356 A1 WO2018044356 A1 WO 2018044356A1
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WO
WIPO (PCT)
Prior art keywords
deprotection
coupling
solid phase
cycle
phase peptide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2017/028254
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English (en)
French (fr)
Inventor
Jonathan M. Collins
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CEM Corp
Original Assignee
CEM Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2016/058181 external-priority patent/WO2017070512A1/en
Priority claimed from US15/490,090 external-priority patent/US10239914B2/en
Application filed by CEM Corp filed Critical CEM Corp
Priority to EP17847113.2A priority Critical patent/EP3507299B1/en
Priority to DK17847113.2T priority patent/DK3507299T3/da
Priority to CA3034810A priority patent/CA3034810C/en
Priority to JP2019511957A priority patent/JP2019530659A/ja
Priority to CN201780053940.9A priority patent/CN109715647A/zh
Publication of WO2018044356A1 publication Critical patent/WO2018044356A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/045—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers using devices to improve synthesis, e.g. reactors, special vessels
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • washing is required between each step to completely remove the reagents previously used so that they don't undesirably participate in the next step.
  • This typically involves "insertions” which refer to the incorporation of an extra amino acid. This is thought to occur through either residual base removing the protecting group (Fmoc) on an amino acid recently coupled thereby allowing a second amino acid to "insert”; or through residual activated amino acid left behind during the subsequent deprotection step which could couple to deblocked sites thereby "inserting" an extra amino acid from the previous step. It was recently shown, however, that washing after the coupling step was not required for the successful synthesis of peptides.
  • the invention is a method of deprotection in solid phase peptide synthesis in which the improvement comprises adding the deprotection composition in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated amino acid from the preceding coupling cycle; and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle; and with the coupling solution at least 30°C.
  • the invention is a method of deprotection in solid phase peptide synthesis in which the improvement comprises adding the deprotection composition in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated amino acid from the preceding coupling cycle; and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle which removes at least 50% of the volume of the previous cycle coupling solution; and with the coupling solution at a temperature of at least 30°c.
  • Figure 1 illustrates a traditional SPPS Cycle
  • FIG. 2 illustrates more recent SPPS Cycles for High Efficiency Solid Phase Peptide Synthesis (HE -SPPS)
  • Figure 3 illustrates in- situ solvent recycling process for solid phase peptide synthesis.
  • This invention presents a novel process whereby the coupling and deprotection steps occur within the same solvent.
  • concentrated base is added directly to the resin coupling solution after a desired period of time for the coupling to occur.
  • the deprotection step is then immediately started when the base is added. Therefore, the onset of the deprotection step is immediately after the coupling step without any time delay.
  • This new process provided a significant reduction in standard cycle time (2 minutes 57 seconds) from (a) - elimination of the coupling drain time, (b) - elimination of the deprotection delivery time between steps, and (c) - elimination of the temperature ramp time for the deprotection step thereby allowing a shorter deprotection time to be used. Additionally, significant solvent savings were possible with the complete elimination of the deprotection solvent during each cycle.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Peptides Or Proteins (AREA)
PCT/US2017/028254 2016-09-03 2017-04-19 In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures Ceased WO2018044356A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP17847113.2A EP3507299B1 (en) 2016-09-03 2017-04-19 In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures
DK17847113.2T DK3507299T3 (da) 2016-09-03 2017-04-19 Fremgangsmåde til genvinding af in-situ-opløsningsmiddel til fastfasepeptidsyntese ved forhøjede temperaturer
CA3034810A CA3034810C (en) 2016-09-03 2017-04-19 In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures
JP2019511957A JP2019530659A (ja) 2016-09-03 2017-04-19 高温での固相ペプチド合成のためのインサイツ溶媒リサイクル法
CN201780053940.9A CN109715647A (zh) 2016-09-03 2017-04-19 用于高温固相肽合成的原位溶剂回收方法

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201662383397P 2016-09-03 2016-09-03
US62/383,397 2016-09-03
USPCT/US2016/058181 2016-10-21
PCT/US2016/058181 WO2017070512A1 (en) 2015-10-23 2016-10-21 Improvements in solid phase peptide synthesis
US15/299,931 2016-10-21
US15/299,931 US10125163B2 (en) 2015-10-23 2016-10-21 Solid phase peptide synthesis
US15/490,090 US10239914B2 (en) 2015-10-23 2017-04-18 In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures
US15/490,090 2017-04-18

Publications (1)

Publication Number Publication Date
WO2018044356A1 true WO2018044356A1 (en) 2018-03-08

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2017/028254 Ceased WO2018044356A1 (en) 2016-09-03 2017-04-19 In-situ solvent recycling process for solid phase peptide synthesis at elevated temperatures

Country Status (6)

Country Link
EP (1) EP3507299B1 (enExample)
JP (1) JP2019530659A (enExample)
CN (1) CN109715647A (enExample)
CA (1) CA3034810C (enExample)
DK (1) DK3507299T3 (enExample)
WO (1) WO2018044356A1 (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024058924A1 (en) * 2022-09-16 2024-03-21 Cem Corporation Peptide synthesis processes
USRE49961E1 (en) 2016-10-21 2024-05-07 Cem Corporation Solid phase peptide syntheses

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140275481A1 (en) * 2013-03-15 2014-09-18 Massachusetts Institute Of Technology Solid phase peptide synthesis processes and associated systems

Family Cites Families (9)

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US20040238794A1 (en) * 2003-05-30 2004-12-02 Karandikar Prashant G. Microwave processing of composite bodies made by an infiltration route
US7393920B2 (en) * 2003-06-23 2008-07-01 Cem Corporation Microwave-assisted peptide synthesis
US7902488B2 (en) * 2003-06-23 2011-03-08 Cem Corporation Microwave-assisted peptide synthesis
WO2006026184A2 (en) * 2004-08-20 2006-03-09 Washington University Blood brain barrier permeation peptides
US8314208B2 (en) * 2006-02-10 2012-11-20 Cem Corporation Microwave enhanced N-fmoc deprotection in peptide synthesis
CA2808270A1 (en) * 2010-08-16 2012-02-23 Cem Corporation Water soluble solid phase peptide synthesis
US8906681B2 (en) * 2011-08-02 2014-12-09 The Scripps Research Institute Reliable stabilization of N-linked polypeptide native states with enhanced aromatic sequons located in polypeptide tight turns
EP2703073A1 (en) * 2012-08-31 2014-03-05 Biotage AB Apparatus and method for solid phase synthesis
EP3365352A4 (en) * 2015-10-23 2019-06-05 CEM Corporation IMPROVEMENTS OF SOLID PHASE PEPTIDE SYNTHESIS

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140275481A1 (en) * 2013-03-15 2014-09-18 Massachusetts Institute Of Technology Solid phase peptide synthesis processes and associated systems

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
COLLINS, J. M. ET AL.: "High-efficiency solid phase peptide synthesis (HE-SPPS", ORGANIC LETTERS, vol. 16, no. 3, 24 January 2014 (2014-01-24), pages 940 - 943, XP055274270, Retrieved from the Internet <URL:http://pubs.acs.org/doi/abs/10.1021/0l4036825> *
E. ATHERTONN. L. BENOITONE. BROWNR. SHEPPARDB. J. WILLIAMS: "Racemization of Activated, Urethane-protected Amino-acids by p-Dimethylaminopyridine. Significance in Solid Phase Peptide Synthesis", J.C.S. CHEM. COMM., 1981, pages 336 - 337
J. COLLINSK. PORTERS. SINGHG. VANIER: "High-Efficiency Solid Phase Peptide Synthesis (HE-SPPS", ORG. LETT., vol. 16, 2014, pages 940 - 943

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USRE49961E1 (en) 2016-10-21 2024-05-07 Cem Corporation Solid phase peptide syntheses
WO2024058924A1 (en) * 2022-09-16 2024-03-21 Cem Corporation Peptide synthesis processes

Also Published As

Publication number Publication date
JP2019530659A (ja) 2019-10-24
CN109715647A (zh) 2019-05-03
EP3507299A4 (en) 2020-04-29
DK3507299T3 (da) 2022-09-05
CA3034810A1 (en) 2018-03-08
EP3507299A1 (en) 2019-07-10
CA3034810C (en) 2023-09-05
EP3507299B1 (en) 2022-07-27

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