2 research outputs found
Native Chemical Ligation–Photodesulfurization in Flow
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
Total Synthesis of Teixobactin
The first total synthesis of the
cyclic depsipeptide natural product
teixobactin is described. Synthesis was achieved by solid-phase peptide
synthesis, incorporating the unusual l-<i>allo</i>-enduracididine as a suitably protected synthetic cassette and employing
a key on-resin esterification and solution-phase macrolactamization.
The synthetic natural product was shown to possess potent antibacterial
activity against a range of Gram-positive pathogenic bacteria, including
a virulent strain of <i>Mycobacterium tuberculosis</i> and
methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)