ABSTRACT
Background. Many occupational therapists make home modification recommendations; however, it is unknown if sustainability considerations (i.e., economic, social, and environmental) are contemplated during this process. Purpose. To understand occupational therapists' perceptions regarding the sustainability of home modifications. Method. This study adopted a qualitative description approach. Researchers utilized semistructured interviews as the primary means of data collection. Findings. The ten female occupational therapists interviewed had three or more years of experience working with home modifications. The analysis identified three themes: It's not easy being green: environmental sustainability, stretching a dollar: financial inequities, and barriers and benefits in the home modification process. Implications. Findings suggest OTs have a varied and a general understanding of how to implement sustainability concepts in their practice. There is also a need to make access to home modifications more equitable. Further research is needed to build a more robust understanding of how OT recommended home modifications can contribute to sustainability.
Subject(s)
Occupational Therapy , Humans , Occupational Therapy/organization & administration , Female , Qualitative Research , Occupational Therapists/psychology , Housing , Interviews as Topic , Attitude of Health Personnel , AdultABSTRACT
Epigenetic regulation of gene expression is in part controlled by post-translational modifications on histone proteins. Histone methylation is a key epigenetic mark that controls gene transcription and repression. There are five human polycomb paralog proteins (Cbx2/4/6/7/8) that use their chromodomains to recognize trimethylated lysine 27 on histone 3 (H3K27me3). Recognition of the methyllysine side chain is achieved through multiple cation-pi interactions within an 'aromatic cage' motif. Despite high structural similarity within the chromodomains of this protein family, they each have unique functional roles and are linked to different cancers. Selective inhibition of different CBX proteins is desirable for both fundamental studies and potential therapeutic applications. We report here on a series of peptidic inhibitors that target certain polycomb paralogs. We have identified peptidic scaffolds with sub-micromolar potency, and will report examples that are pan-specific and that are partially selective for individual members within the family. These results highlight important structure-activity relationships that allow for differential binding to be achieved through interactions outside of the methyllysine-binding aromatic cage motif.
Subject(s)
Peptides/pharmacology , Polycomb-Group Proteins/antagonists & inhibitors , Dose-Response Relationship, Drug , Humans , Molecular Structure , Peptides/chemical synthesis , Peptides/chemistry , Polycomb-Group Proteins/genetics , Structure-Activity RelationshipABSTRACT
The polycomb paralogs CBX2, CBX4, CBX6, CBX7, and CBX8 are epigenetic readers that rely on "aromatic cage" motifs to engage their partners' methyllysine side chains. Each CBX carries out distinct functions, yet each includes a highly similar methyllysine-reading chromodomain as a key element. CBX7 is the only chromodomain that has yet been targeted by chemical inhibition. We report a small set of peptidomimetic agents in which a simple chemical modification switches the ligands from one with promiscuity across all polycomb paralogs to one that provides selective inhibition of CBX6. The structural basis for this selectivity, which involves occupancy of a small hydrophobic pocket adjacent to the aromatic cage, was confirmed through molecular dynamics simulations. Our results demonstrate the increases in affinity and selectivity generated by ligands that engage extended regions of chromodomain binding surfaces.
