Development of a novel peptide inhibitor of subtilisin BPN'.

Proteinaceous protease inhibitors can strongly and specifically inhibit cognate proteases, but their use as pharmaceuticals is limited by their size. As such, the development of effective protease peptide inhibitors would be beneficial for biochemical studies and drug discovery. In this study, we applied a phage display system to select subtilisin BPN'-binding peptides and evaluated their inhibitory activities against subtilisin BPN'. A 12mer peptide with an intramolecular disulfide bond inhibited subtilisin BPN' (Ki value of 13.0 nm). Further mutational analyses of the peptide resulted in the development of a short peptide inhibitor against subtilisin BPN' that showed high inhibitory activity and binding affinity (Ki value of 0.30 nm). This activity was found to be derived from the conformational rigidity caused by the intramolecular disulfide bond and the small residue at the P1' site and from the interaction of the P4 and P6' residues with subtilisin BPN'.

Experiences of advance care planning for community-dwelling older people: a qualitative systematic review protocol.

OBJECTIVE: The objective of this qualitative systematic review is to evaluate and synthesize the recent literature on advance care planning (ACP) experiences of community-dwelling older people in interaction with community healthcare professionals. INTRODUCTION: The importance of healthcare professionals initiating ACP with their patients and clients has been reported. However, older people who live in the community have fewer opportunities to have discussions regarding ACP with healthcare professionals compared with those who live in other settings. Timely initiation of ACP and sustainable discussion among older people, families, and community healthcare professionals is expected, which may lead to improved palliative and end-of-life care in the community. INCLUSION CRITERIA: This review will consider studies that include individuals older than 60 years living in their homes in the community. Studies published in English or Japanese that focus on qualitative data and are published from 1999 to present will be considered. METHODS: The key information sources to be searched are: MEDLINE, CINAHL, Embase, PsycINFO, JSTORE, Scopus, Japan Medical Abstract Society, CiNii for published papers, and Google Scholar, ProQuest Dissertations & Theses Global, and MedNar for unpublished papers and gray literature. Eligible studies will be critically appraised using the standardized JBI tool. Qualitative research findings will be pooled using the meta-aggregation approach. Then the final synthesized findings will be graded according to the ConQual approach for establishing confidence in the output of qualitative research synthesis and presented in a Summary of Findings.