RESUMO
In the 1980s, virus inactivation steps were implemented into the manufacturing of biopharmaceuticals in response to earlier unforeseen virus transmissions. The most effective inactivation process for lipid-enveloped viruses is the treatment by a combination of detergents, often including Triton X-100 (TX-100). Based on recent environmental concerns, the use of TX-100 in Europe will be ultimately banned, which forces the pharmaceutical industry, among others, to switch to an environmentally friendly alternative detergent with fully equivalent virus inactivation performance such as TX-100. In this study, a structure-activity relationship study was conducted that ultimately led to the synthesis of several new detergents. One of them, named "Nereid," displayed inactivation activity fully equivalent to TX-100. The synthesis of this replacement candidate has been optimized to allow for the production of several kg of detergent at lab scale, to enable the required feasibility and comparison virus inactivation studies needed to support a potential future transition. The 3-step, chromatography-free synthesis process described herein uses inexpensive starting materials, has a robust and simple work-up, and allows production in a standard organic laboratory to deliver batches of several hundred grams with >99% purity.
Assuntos
Detergentes/síntese química , Detergentes/farmacologia , Herpesvirus Suídeo 1/efeitos dos fármacos , Inativação de Vírus/efeitos dos fármacos , Animais , Chlorocebus aethiops , Detergentes/química , Herpesvirus Suídeo 1/fisiologia , Octoxinol , Fenol/análise , Células VeroRESUMO
Chemical probes were devised and evaluated for the capture of biosynthetic intermediates involved in the bio-assembly of the nonribosomal peptide echinomycin. Putative intermediate peptide species were isolated and characterised, providing fresh insights into pathway substrate flexibility and paving the way for novel chemoenzymatic approaches towards unnatural peptides.
Assuntos
Equinomicina/biossíntese , Sondas Moleculares/análise , Equinomicina/química , Sondas Moleculares/química , Estrutura MolecularRESUMO
Correction for 'Novel chemical probes for the investigation of nonribosomal peptide assembly' by Y. T. Candace Ho et al., Chem. Commun., 2017, 53, 7088-7091.