Anticancer drugs

Light-activated destruction of cancer cell nuclei by platinum diazide complexes. Bednarski, P. J. et al. Chem. Biol. 13, 61–67 (2006)

To improve the specificity and safety of platinum-based anticancer drugs, Bednarski et al. used light to induce photochemical changes in non-toxic platinum prodrugs which then release the active drug within the tumour. Two photolabile prodrug complexes of cisplatin and an analogue were evaluated for their capacity to inhibit the growth of human bladder cancer cells in light and dark conditions. Light activation of the prodrugs caused adducts in tumour DNA more quickly than cisplatin and caused disintegration of cancer cell nuclei. The prodrugs were also active against cisplatin-resistant cell lines, and could prove useful against several tumour types that are light-accessible.

Model organisms

Conservation of gene expression signatures between zebrafish and human liver tumors and tumor progression. Lam, S. H. et al. Nature Biotechnol. 24, 73–75 (2006)

Because little is known about how similar zebrafish and human cancers are at the molecular level, Lam and colleagues set out to identify gene signatures for particular tumour phenotypes in zebrafish and humans, and compare their similarity. They generated liver tumours in zebrafish and identified a set of genes that were differentially expressed in these tumours compared with normal liver tissues. The deregulated genes were found to be homologues of human proteins involved in processes related to tumour progression, such as cell-cycle regulation and DNA repair, indicating that the zebrafish tumours have similar hallmark genetic changes to human tumours.

Chemical biology

SMM-chemokines: a class of unnatural synthetic molecules as chemical probes of chemokine receptor biology and leads for therapeutic development. Kumar, S. et al. Chem. Biol. 13, 69–79 (2006)

Developing selective inhibitors of specific chemokine receptors has proved challenging. This paper describes a method of creating synthetically and modularly modified (SMM)-chemokines using 'total chemical synthesis' to incorporate an unlimited range of unnatural amino acids and chemical modifications into novel peptide ligands. The authors were able to convert the non-selective vMIPII inhibitor into ligands with high selectivity for CXRC4 or CCR5 and improved pharmacokinetic and toxicity profiles.

Mood disorders

Leptin: a potential novel antidepressant. Lu, X. -Y. et al. Proc. Natl Acad. Sci. USA 103, 1593–1598 (2006)

Although leptin is known to be involved in energy homeostasis, it has also recently been implicated in depression. Lu and colleagues now show that circulating leptin is downregulated in rats suffering from conditions that produce behavioural deficits similar to depression. Evaluation of the antidepressant effect of leptin showed that behavioural alterations in the decreased sucrose preference test and the forced swim test were overcome by leptin administration.