title: Aromatic amides and ureas as novel molecular probes for diagnosing disease.
abstract: It is firmly established that control over the three-dimensional shape (i.e., the conformation) of aromatic amides and ureas can be achieved using a variety of methods, all of which rely on the addition of a substituent to a central nitrogen atom; exactly which conformation is adopted in solution can be determined using a variety of analytical techniques, such as: fluorescence, NMR and HPLC. We hypothesise that if the central nitrogen atoms were suitably functionalised with enzyme-cleavable groups, then the associated change in shape could be exploited upon the removal of a group, and these compounds could thus be exploited as diagnostic probes for the detection of analytes (i.e., enzymes) in solution or biological samples. The exquisite selectivity of naturally-occurring enzymes therefore makes it possible that the enzyme-cleavable group could be rationally designed and tailored for each enzyme of interest, thus making an analytical toolkit of diagnostic probes for detecting enzymes which are over-expressed in disease. If the sensitivity of such probes was sufficiently low enough, then they could potentially be used to detect the on-set of disease in a non-invasive manner from bodily fluids.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Maudland Building, Preston, Lancashire PR1 2HE, UK.
authors.forename: Samridhi
authors.initials: S
authors.lastname: Lal
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Maudland Building, Preston, Lancashire PR1 2HE, UK. Electronic address: tjsnape@uclan.ac.uk.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Snape
mesh_terms: D000577:Amides / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D064907:Diagnostic Uses of Chemicals; D004798:Enzymes; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D011487:Protein Conformation; D012996:Solutions; D014508:Urea / Q000737:chemistry*
chemical_list: D000577:Amides; D064907:Diagnostic Uses of Chemicals; D004798:Enzymes; D015335:Molecular Probes; D009930:Organic Chemicals; D012996:Solutions; D014508:Urea; D009584:Nitrogen