Medda, F., Smith, B., Gokhale, V., Shaw, A. Y., Dunckley, T., & Hulme, C. (2013). Beyond secretases: Kinase inhibitors for the treatment of Alzheimer's disease. Annual Reports in Medicinal Chemistry, 48, 57-71.
Abstract:
Alzheimer's disease (AD) is the most prevalent form of dementia in old age. Recent data indicate that 24.3 million people worldwide suffer from AD. Hyperphosphorylation of tau, a protein normally involved in microtubule stabilization, has been identified as an important pathological contributor to AD development. In AD brains, hyperphosphorylation of tau leads to its aggregation, misfolding, and formation of neurofibrillary tangles, one common hallmark of AD. Specific protein kinases, such as GSK-3β, CDK5, and DYRK1A, are involved in tau hyperphosphorylation and have been identified as potential targets for the development of novel therapeutic agents for the treatment of AD cognitive deficits. We herein review the current state of the art in the development of small molecule inhibitors of GSK-3β, CDK5, DYRK1A, and other protein kinases involved in tau phosphorylation. Only recently developed compounds with cellular and/or in vivo activity will be discussed. © 2013 Elsevier Inc.
Baldwin, J. E., Claridge, T. D., Hulme, C., Rodger, A., & Schofield, C. J. (1994). Comments on the use of a dichromophoric circular dichroism assay for the identification of β-turns in peptides. International Journal of Peptide and Protein Research, 43(2), 180-184.
PMID: 8200737;Abstract:
Use of the dichromophoric CD assay for β-turn formation in peptide sequences has been investigated. The assay involves the observation of Cotton effects in CD spectra, originating from the approach of N- and C-terminal aromatic chromophores in tetrapeptides. The approach of the chromophores was believed to be brought about by a β-turn in the peptide structure. Our investigations were paralleled by NMR studies which revealed the presence of a previously unreported hydrogen bond in the β-turn conformers, which appears to play a role in the generation of the observed Cotton effects. This suggests caution in the use of the CD technique alone as an assay for β- turn conformers in peptides.
Dömling, A., & Hulme, C. (2011). Molecular Diversity: Editorial. Molecular Diversity, 15(1), 1-2.
Hulme, C., Pinho, L., Martinez-Arisa, G., & Day, K. (2016). Synthesis of Fluorescent Heterocycles via a Knoevenagel/ [4+1]-Cycloaddition Cascade Using Acetyl Cyanide.. Organic and Bio-molecular Chemistry.
Hulme, C., Shaw, A. Y., McLaren, J. A., Nichol, G. S., & Hulme, C. -. (2012). Hydrazine-mediated cyclization of Ugi products to synthesize novel 3-hydroxypyrazoles. Tetrahedron letters, 53(21).
This report discloses a novel concise synthesis of a series of 3-hydroxypyrazoles 5 via a tandem Ugi/debenzylation /hydrazine-mediated cyclization sequence. Herein, n-butyl isocyanide 4b was utilized as an alternative to classical convertible isocyanides enabling high yielding hydrazine-mediated cyclization. Taken together, a novel class of 3-hydroxypyrazoles 5a-5i was synthesized with potential to be of interest in future library enrichment strategies.