Ag(I)-promoted fragment coupling of peptide thioamides.

Despite advances in solid phase peptide synthesis and peptide ligation, challenges remain in the assembly of polypeptides through coupling of peptide fragments. Herein we describe a new method for peptide fragment coupling employing the Ag(I)-promoted transformation of peptide thioamides. This process proceeds an isoimide-tethered intermediate, which undergoes an O-N acyl transfer to generate the polypeptide.

Late-Stage Pd(II)-Catalyzed C(sp)-H Functionalization of Peptides Directed by a Removable, Backbone-Inserted Amidoxime Ether.

Palladium(II)-catalyzed C-H functionalization has attracted considerable attention as a pathway to late-stage modification of peptides. Herein, we report the Pd-catalyzed C(sp)-H arylation of peptides directed by an amidoxime ether, which can be easily incorporated into peptides at any amide bond. Site- and stereoselective arylation of peptides has been achieved, including unprecedented functionalization of internal residues of native peptides.

A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.

The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity.

"Do they think I'm good enough?": General practitioners' experiences when treating doctor-patients.

Background: When doctors seek medical care, there is evidence that the treating doctor can struggle to provide optimal treatment. Guidelines state that doctor-patients should be treated like any other patient, but this is challenging for the treating doctor. This study set out to explore both the positive experiences general practitioners (GPs) have when caring for doctor-patients, and the challenges they confront.