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Untapped Opportunities of Resin‐to‐Resin Transfer Reactions (RRTR) for the Convergent Assembly of Multivalent Peptide Conjugates
Author(s) -
Verzele Dieter,
Ruiz García Yara,
Madder Annemieke
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000434
Subject(s) - bioconjugation , bottleneck , context (archaeology) , chemistry , conjugate , peptide , combinatorial chemistry , condensation , steric effects , tetrapeptide , computer science , organic chemistry , biochemistry , mathematics , biology , paleontology , mathematical analysis , physics , embedded system , thermodynamics
Handling of the individual fragments remains a bottleneck in the convergent assembly of peptides. Overlooked since the emergence of ligation chemistries during the past two decades, so‐called resin‐to‐resin transfer reactions (RRTR) are here described as a strategic shortcut in this context. Condensation of the involved moieties at an acceptor resin is facilitated by shuttling peptide segments directly from a donor resin in a one‐pot fashion. The straightforward synthesis of a sterically constrained 13‐mer peptidosteroid model illustrates the utility of this approach, presenting the first successful application of the RRTR methodology in the field of multivalent design and bioconjugation. Relying on established procedures to generate, monitor and isolate intermediates and products, the solid‐phase nature of the entire strategy allows for the fast construction of polypeptide adducts and libraries thereof. As such, a rejuvenated use and new opportunities for RRTR are reported.