1611469-02-3Relevant articles and documents
Peptide Ligation at High Dilution via Reductive Diselenide-Selenoester Ligation
Chisholm, Timothy S.,Kulkarni, Sameer S.,Hossain, Khondker R.,Cornelius, Flemming,Clarke, Ronald J.,Payne, Richard J.
supporting information, p. 1090 - 1100 (2020/01/31)
Peptide ligation chemistry has revolutionized protein science by providing access to homogeneously modified peptides and proteins. However, lipidated polypeptides and integral membrane proteins- A n important class of biomolecules-remain enormously challenging to access synthetically owing to poor aqueous solubility of one or more of the fragments under typical ligation conditions. Herein we describe the advent of a reductive diselenide-selenoester ligation (rDSL) method that enables efficient ligation of peptide fragments down to low nanomolar concentrations, without resorting to solubility tags or hybridizing templates. The power of rDSL is highlighted in the efficient synthesis of the FDA-approved therapeutic lipopeptide tesamorelin and palmitylated variants of the transmembrane lipoprotein phospholemman (FXYD1). Lipidation of FXYD1 was shown to critically modulate inhibitory activity against the Na+/K+ pump.
NEW SYNTHETIC METHODS USING NATIVE CHEMICAL LIGATION IN FLOW
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Page/Page column 17; 78, (2019/12/15)
The disclosure relates to the synthesis of amide containing compounds in flow. In particular, the disclosure relates to the synthesis of polypeptides via native chemical ligation in flow. The disclosure also relates to selective desulfurization or deselen
Native Chemical Ligation-Photodesulfurization in Flow
Chisholm, Timothy S.,Clayton, Daniel,Dowman, Luke J.,Sayers, Jessica,Payne, Richard J.
, p. 9020 - 9024 (2018/08/03)
Native chemical ligation (NCL) combined with desulfurization chemistry has revolutionized the way in which large polypeptides and proteins are accessed by chemical synthesis. Herein, we outline the use of flow chemistry for the ligation-based assembly of polypeptides. We also describe the development of a novel photodesulfurization transformation that, when coupled with flow NCL, enables efficient access to native polypeptides on time scales up to 2 orders of magnitude faster than current batch NCL-desulfurization methods. The power of the new ligation-photodesulfurization flow platform is showcased through the rapid synthesis of the 36 residue clinically approved HIV entry inhibitor enfuvirtide and the peptide diagnostic agent somatorelin.
Trifluoroethanethiol: An additive for efficient one-pot peptide ligation - Desulfurization chemistry
Thompson, Robert E.,Liu, Xuyu,Alonso-García, Noelia,Pereira, Pedro José Barbosa,Jolliffe, Katrina A.,Payne, Richard J.
, p. 8161 - 8164 (2014/06/24)
Native chemical ligation followed by desulfurization is a powerful strategy for the assembly of proteins. Here we describe the development of a high-yielding, one-pot ligation-desulfurization protocol that uses trifluoroethanethiol (TFET) as a novel thiol additive. The synthetic utility of this TFET-enabled methodology is demonstrated by the efficient multi-step one-pot syntheses of two tick-derived proteins, chimadanin and madanin-1, without the need for any intermediary purification.
