Matthew A. Jones

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Von Hippel-Lindau (VHL) disease was initially reported to be linked to the RAF1 oncogene (3p25). We have ascertained and sampled two large multigenerational VHL families for linkage studies, in order to confirm the localization of the VHL gene as a prelude to fine mapping studies. The probes used in the analysis were p627 (RAF1) and pHeA12 (thyroid hormone(More)
The rising and setting of the sun marks a transition between starkly contrasting environmental conditions for vegetative life. Given these differing diurnal and nocturnal environmental factors and the inherent regularity of the transition between the two, it is perhaps unsurprising that plants have developed an internal timing mechanism (known as a(More)
PURPOSE We used sheep with an autosomal dominant gene for cortical cataract as an animal model to evaluate novel macrocyclic calpain inhibitors with potential for the medical treatment of human cataract. METHODS The macrocyclic aldehyde, CAT811, identified previously as a calpain inhibitor that prevents calcium-induced opacification in cultured sheep(More)
The design and elaboration of a series of macrocyclic templates that exhibit a propensity to adopt a beta-strand-like peptide-backbone conformation led to potent and selective inhibitors of calpain 2. Macrocycle 1 retarded calcium-induced opacification in an ovine-lens culture assay and is a lead compound for the development of a drug for cataract(More)
Studies of 17 analoges of 3 (SJA6017) in an in silico calpain model are reconciled to measured IC(50) values against ovine calpain. The studies validate the potential of the "model" and criteria established for inhibition as a tool to select structures for synthesis to test as calpain inhibitors. Using this screening methodology of virtual libraries led us(More)
Two new series of 15-membered macrocyclic peptidomimetics, in which the P1 and P3 residues of the peptide backbone are linked by a bridge containing a 1,4-disubstituted 1H-imidazole, are reported. The structure with an aldehyde at the C-terminus and the imidazole at P3, i.e., 4c, shows significant inhibitory activity against calpain 2, with an IC(50) value(More)
PURPOSE The aim of this study is to evaluate the therapeutic potential of a newly synthesized calpain inhibitor, CAT0059, using a naturally occurring in vivo sheep cataract model. METHODS The selectivity of CAT0059 was investigated by an in vitro protease assay. The efficacy of CAT0059 in preventing proteolysis of lens cytoskeletal proteins by calpain 2(More)
The occurrence of spinal deformity in aquaculture can be considerable, and a high rate of deformity has been suggested in triploid smolts in Tasmania. However, the physiological performance of fish with skeletal deformities has not been addressed. The swimming performance and oxygen consumption of triploid Atlantic salmon smolts with either a vertebral(More)
We report the synthesis of macrocycles 1-6 via ring closing metathesis of dienes 7-12. Addition of chlorodicyclohexylborane to thermal and microwave assisted RCM of dienes 8 and 9 markedly improves the yield. The geometric isomers of macrocycles 1-3 and 5 have been assigned using X-ray crystallography and NMR.
The T-cell receptor of a CD8(+) T-cell recognises peptide epitopes bound by class I major histocompatibility complex (MHC) glycoproteins presented in a groove on their upper surface. Within the groove of the MHC molecule are 6 pockets, two of which mostly display a high degree of specificity for binding amino acids capable of making conserved and(More)