ABSTRACT
The development of synthetic chemical probes for the detection of enzymes is extremely important for biological, medicinal, and industrial applications. Here we report the synthesis of an array of novel glycosylated Tb(iii) complexes, their photophysical properties in solution, and their ability to function as luminescent probes for observing glycosidase enzyme activity in real time. Our initial studies into the application of these complexes for the detection of the Concanavalin A (ConA) lectin is also reported, highlighting the broad scope of these novel chemical probes.
Subject(s)
Enzyme Assays/methods , Glycoside Hydrolases/metabolism , Heterocyclic Compounds/chemistry , Luminescent Agents/chemistry , Terbium/chemistry , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Cyclams , Glycoside Hydrolases/analysis , Glycosylation , Heterocyclic Compounds/chemical synthesis , Humans , Luminescence , Luminescent Agents/chemical synthesis , Luminescent Measurements/methodsABSTRACT
The emergence of synthetic glycoconjugates as chemical probes for the detection of glycosidase enzymes has resulted in the development of a range of useful chemical tools with applications in glycobiology, biotechnology, medical and industrial research. Critical to the function of these probes is the preparation of substrates containing a glycosidic linkage that when activated by a specific enzyme or group of enzymes, irreversibly releases a reporter molecule that can be detected. Starting from the earliest examples of colourimetric probes, increasingly sensitive and sophisticated substrates have been reported. In this review we present an overview of the recent advances in this field, covering an array of strategies including chromogenic and fluorogenic substrates, lanthanide complexes, gels and nanoparticles. The applications of these substrates for the detection of various glycosidases and the scope and limitations for each approach are discussed.
Subject(s)
Glycoside Hydrolases/metabolism , Molecular Probes/metabolism , Chromogenic Compounds/chemistry , Chromogenic Compounds/metabolism , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Gels/chemistry , Gels/metabolism , Glycoside Hydrolases/chemistry , Lanthanoid Series Elements/chemistry , Lanthanoid Series Elements/metabolism , Molecular Probes/chemistry , Nanoparticles/chemistry , Nanoparticles/metabolism , Substrate SpecificityABSTRACT
We have developed a copper-catalyzed process for the coupling of aldehydes, amines, and boronic acids. This allows greater reactivity with simple aryl boronic acids and allows coupling reactions to proceed that previously failed. Initial mechanistic studies support a process involving transmetalation from boron to copper.
Subject(s)
Amines/chemistry , Boronic Acids/chemistry , Boronic Acids/chemical synthesis , Copper/chemistry , Catalysis , Esters , Molecular StructureABSTRACT
Objectives. Patient experiences of structured heart failure rehabilitation and their views on the important components of heart failure services were examined. Methods. Focus groups were conducted with fifteen participants (men, n = 12) attending one of two heart failure rehabilitation programmes. Sessions were guided by a semistructured interview schedule covering participants' experiences of the programme, maintenance, and GP role. Focus group transcripts were analysed qualitatively. Results. Participants indicated that rehabilitation programmes substantially met their needs. Supervised exercise sessions increased confidence to resume physical activity, while peer-group interaction and supportive medical staff improved morale. However, once the programme ended, some participants' self-care motivation lapsed, especially maintenance of an exercise routine. Patients doubted their GPs' ability to help them manage their condition. Conclusion. Structured rehabilitation programmes are effective in enabling patients to develop lifestyle skills to live with heart failure. However, postrehabilitation maintenance interventions are necessary to sustain patients' confidence in disease self-management.
