Diffusion-enhanced amide bond formation on a solid support

Johnny N. Naoum , Israel Alshanski , Agata Gitlin-Domagalska , Moshe Bentolila , Chaim Gilon , Mattan Hurevich

Abstract

Mixing of polystyrene resins in solid-phase synthesis is performed by shaking or gentle agitation of the reaction vessel to avoid breaking the brittle beads. These mixing strategies result in poor diffusion to and into the beads. Using a large excess of reagents is the common way to compensate for these deficiencies. We use fast overhead stirring for performing coupling reactions on a solid support. We show that fast overhead stirring enhances the efficiency of amide bond formation on the solid support compared to the state-of-the-art mixing method, while preserving the integrity of the beads. We find that fast overhead stirring minimizes the effect of decomposition of the activated species by increasing the diffusion-dependent coupling reaction. This allows decreasing the excess of reagents used for the multistep synthesis of peptides, thus providing a greener and more sustainable alternative for peptide synthesis on solid supports.
Author Johnny N. Naoum
Johnny N. Naoum,,
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, Israel Alshanski
Israel Alshanski,,
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, Agata Gitlin-Domagalska (FCh / DMB / LBCh)
Agata Gitlin-Domagalska,,
- Laboratory of Bioorganic Chemistry
, Moshe Bentolila
Moshe Bentolila,,
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, Chaim Gilon
Chaim Gilon,,
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, Mattan Hurevich
Mattan Hurevich,,
-
Journal seriesOrganic Process Research & Development, ISSN 1083-6160, e-ISSN 1520-586X, (N/A 100 pkt)
Issue year2019
Vol23
No12
Pages2733-2739
Publication size in sheets0.5
Keywords in Englishpeptides, solid-phase synthesis, amide bond formation, sustainable chemistry, diffusion
ASJC Classification1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry
DOIDOI:10.1021/acs.oprd.9b00398
URL https://doi.org/10.1021/acs.oprd.9b00398
Languageen angielski
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 28-04-2020, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 0.978; WoS Impact Factor: 2018 = 3.327 (2) - 2018=3.171 (5)
Citation count*1 (2020-05-19)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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