Stabilization of Peptide Vesicles by Introducing Inter-Peptide Disulfide Bonds

PURPOSE: Previously, we have shown that the amphiphilic oligopeptide SA2 (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) spontaneously self-assemble into nano-sized vesicles in aqueous environment. Relative weak individual intermolecular interactions dominate such oligopeptide assemblies. In this study we aimed at improving the stability of such peptide vesicles by covalently crosslinking the oligopeptide vesicles using disulfide bonds. Two and three cysteines were introduced in the SA2 peptide sequence to allow crosslinking (Ac-Ala-Cys-Val-Cys-Leu-(Leu/Cys)-Leu-Trp-Glu-Glu-COOH). RESULTS: Upon disulfide formation the crosslinked vesicles remained stable under conditions that disrupted the non-crosslinked peptide vesicles. The stabilized vesicles were more closely examined in terms of particle size (distribution) using atomic force microscopy, cryogenic electron microscopy, as well as dynamic light scattering analysis, showing an average particle radius in number between 15 and 20 nm. Using entrapment of calcein it was shown that intermolecular crosslinking of peptides within the vesicles did not affect the permeability for calcein. CONCLUSION: Introduction of cysteines into the hydrophobic domain of the SA2 amphiphilic oligopeptides is a feasible strategy for crosslinking the peptide vesicles. Such small crosslinked oligopeptide vesicles may hold promise for drug delivery applications

Manchester Clinical Placement Index (MCPI): Conditions for medical students’ learning in hospital and community placements

The drive to quality-manage medical education has created a need for valid measurement instruments. Validity evidence includes the theoretical and contextual origin of items, choice of response processes, internal structure, and interrelationship of a measure’s variables. This research set out to explore the validity and potential utility of an 11-item measurement instrument, whose theoretical and empirical origins were in an Experience Based Learning model of how medical students learn in communities of practice (COPs), and whose contextual origins were in a community-oriented, horizontally integrated, undergraduate medical programme. The objectives were to examine the psychometric properties of the scale in both hospital and community COPs and provide validity evidence to support using it to measure the quality of placements. The instrument was administered twice to students learning in both hospital and community placements and analysed using exploratory factor analysis and a generalizability analysis. 754 of a possible 902 questionnaires were returned (84% response rate), representing 168 placements. Eight items loaded onto two factors, which accounted for 78% of variance in the hospital data and 82% of variance in the community data. One factor was the placement learning environment, whose five constituent items were how learners were received at the start of the placement, people’s supportiveness, and the quality of organisation, leadership, and facilities. The other factor represented the quality of training—instruction in skills, observing students performing skills, and providing students with feedback. Alpha coefficients ranged between 0.89 and 0.93 and there were no redundant or ambiguous items. Generalisability analysis showed that between 7 and 11 raters would be needed to achieve acceptable reliability. There is validity evidence to support using the simple 8-item, mixed methods Manchester Clinical Placement Index to measure key conditions for undergraduate medical students’ experience based learning: the quality of the learning environment and the training provided within it. Its conceptual orientation is towards Communities of Practice, which is a dominant contemporary theory in undergraduate medical education

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG