68 research outputs found
β-Lactamase cleavable antimicrobial peptide–drug conjugates
Antimicrobial resistance attracts a considerable amount of attention as it threatens the efficiency of current antibacterial treatments. Besides a more considerate use of current antibiotics to slow down the spread of antimicrobial resistance, there is ample need for new therapeutic avenues to treat already resistant strains. Here, we describe the use of a cleavable peptide–drug conjugate to target bacteria with diverse resistance strategies. The conjugate consists of three main components: a β-lactamase cleavable linker, a positively charged stapled antimicrobial peptide, and an antibiotic. The linker ensures selective cleavage and provides the prospect of lowering systemic toxicity of the conjugate. The positively charged peptide targets the negatively charged bacterial membrane, and stapling pre-organises it in a helical structure. Finally, the drug provides another, distinct mode of action to the peptide, which should overall reduce the development of resistance. A series of peptides was prepared and the most promising one was then developed into a stapled conjugate. The factors affecting the activity of this conjugate were investigated, proving cleavage by β-lactamase and superior potency compared to the non-cleavable control, as shown by its minimal inhibitory concentrations
Cell-Adhesive Responses to Tenascin-C Splice Variants Involve Formation of Fascin Microspikes
Education for sustainable development (ESD): the turn away from ‘environment’ in environmental education?
This article explores the implications of the shift of environmental education (EE) towards education for sustainable development (ESD) in the context of environmental ethics. While plural perspectives on ESD are encouraged both by practitioners and researchers of EE, there is also a danger that such pluralism may sustain dominant political ideologies and consolidated corporate power that obscure environmental concerns. Encouraging plural interpretations of ESD may in fact lead ecologically ill-informed teachers and students acculturated by the dominant neo-liberal ideology to underprivilege ecocentric perspective. It is argued that ESD, with its focus on human welfare, equality, rights and fair distribution of resources is a radical departure from the aim of EE set out by the Belgrade Charter as well as a distinct turn towards anthropocentrically biased education. This article has two aims: to demonstrate the importance of environmental ethics for EE in general and ESD in particular and to argue in favour of a return to instrumentalism, based on the twinned assumptions that the environmental problems are severe and that education of ecologically minded students could help their resolution
Controlling the contents of microdroplets by exploiting the permeability of pdms
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A novel complexity-to-diversity strategy for the diversity-oriented synthesis of structurally diverse and complex macrocycles from quinine
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