Biophysical fragment screening of the ß1-adrenergic receptor: identification of high affinity arylpiperazine leads using structure-based drug design.

Biophysical fragment screening of a thermostabilized ß1-adrenergic receptor (ß1AR) using surface plasmon resonance (SPR) enabled the identification of moderate affinity, high ligand efficiency (LE) arylpiperazine hits 7 and 8. Subsequent hit to lead follow-up confirmed the activity of the chemotype, and a structure-based design approach using protein-ligand crystal structures of the ß1AR resulted in the identification of several fragments that bound with higher affinity, including indole 19 and quinoline 20. In the first example of GPCR crystallography with ligands derived from fragment screening, structures of the stabilized ß1AR complexed with 19 and 20 were determined at resolutions of 2.8 and 2.7 Å, respectively.

Do healthier nurses make better health promotors? A review of the literature.

This discussion paper draws on a review of the literature to explore factors that might promote or inhibit healthier nursing practice. The term healthier nursing practice, used here, refers to the way commitment to health promoting practices at organisational, professional and personal levels is demonstrated and achieved. Health promotion is a holistic concept that calls for the creation of empowered relationships between self, others, and the environment to improve wellness. Nurses have often struggled to achieve this within their patient encounters and even more so within their own personal and professional life experiences. Two factors were identified in the literature review that appear to significantly impact on this situation, the organisational environment within which nurses practice and their educational exposure to health promoting opportunities. There are a number of parallel processes identified that illustrate the difficulties nurses have in their experiences of working with patients and with themselves in promoting healthier lives. Action learning is advocated as an effective way for nurses to address what are sometimes perceived as being insurmountable barriers to developing health promoting opportunities for patients and the individual nurse.