Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the alpha-conotoxin MII

Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the alpha-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xerl oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.

The multimodal world of medical monitoring displays

A vision of the future of intraoperative monitoring for anesthesia is presented-a multimodal world based on advanced sensing capabilities. I explore progress towards this vision, outlining the general nature of the anesthetist's monitoring task and the dangers of attentional capture. Research in attention indicates different kinds of attentional control, such as endogenous and exogenous orienting, which are critical to how awareness of patient state is maintained, but which may work differently across different modalities. Four kinds of medical monitoring displays are surveyed: (1) integrated visual displays, (2) head-mounted displays, (3) advanced auditory displays and (4) auditory alarms. Achievements and challenges in each area are outlined. In future research, we should focus more clearly on identifying anesthetists' information needs and we should develop models of attention in different modalities and across different modalities that are more capable of guiding design. (c) 2006 Elsevier Ltd. All rights reserved.

The regulatory challenges in engineering a safer tipple

David Nutt asks two very important questions. Can we make alcohol safer? Can we use pharmacology and neuroscience to engineer a safer alternative to alcohol? The answer to the first question is clearly ‘yes’. We can make alcohol safer by encouraging drinkers to consume less alcohol per occasion. That goal can be accomplished by imposing lower taxes on lower alcohol beverages or a volumetric tax on alcoholic beverages (Babor et al., 2003).

Engineering of needle-free physical methods to target epidermal cells for DNA vaccination

A challenge in epidermal DNA vaccination is the efficient and targeted delivery of polynucleotides to immunologically sensitive Langerhans cells. This paper investigates this particular challenge for physical delivery approaches. The skin immunology and material properties are examined in the context of the physical cell targeting requirements of the viable epidermis. Selected current physical cell targeting technologies engineered to meet these needs are examined: needle and syringe; diffusion patches; liquid jet injectors; microneedle arrays/patches; and biolistic particle injection. The operating methods and relative performance of these approaches are discussed, with a comment on potential future developments and technologies. (c) 2005 Elsevier Ltd. All rights reserved.