1044284-90-3Relevant academic research and scientific papers
NEW SYNTHETIC METHODS USING NATIVE CHEMICAL LIGATION IN FLOW
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Page/Page column 13; 72, (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.
supporting information, 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.
Accelerated Protein Synthesis via One-Pot Ligation-Deselenization Chemistry
Mitchell, Nicholas J.,Sayers, Jessica,Kulkarni, Sameer S.,Clayton, Daniel,Goldys, Anna M.,Ripoll-Rozada, Jorge,Barbosa Pereira, Pedro José,Chan, Bun,Radom, Leo,Payne, Richard J.
supporting information, p. 703 - 715 (2017/05/15)
Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future.
