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Abstract

AbstractAntipsychotics in SingaporeDawe and Ratty, Biotechnol. J. 2007, 2, 1344–1352Currently marketed antipsychotics are still accompanied with many side effects and manys patients remain resistant to treatment. Preclinical evaluation of new compounds for psychotic diseases like schizophrenia is not satisfying. A transgenic mouse called chakragati (ckr) exhibits circling and hyperactivity and thus models aspects of schizophrenia. This circling is inhibited by administration of antipsychotic drugs and so lends itself to in vivo prospective screening for novel molecules with antipsychotic‐like activity. In this article Dawe and Ratty from the National University of Singapore review limitations of traditional models and describe the advantages of the ckr mouse, which is the first in vivo approach for screening antipsychotic drug candidates.Defensins in SingaporeVerma et al., Biotechnol. J. 2007, 2, 1353–1359The rapid spread of infections by novel and mutated microbes has given peptide antibiotics a boost in immediacy and urgency to which the scientific community has responded. This largely harbors on the hope that it will be very hard for bacteria to develop resistance, at least quickly, to defensins. This novel class of endogenous antimicrobial peptides has shown great versatility in activity against a diverse range of microorganisms including bacteria, viruses and fungi. The induced bacterial cell lysis seems largely nonspecific and promises to avert the development of resistance. In this review researchers from Singapore describe their successful multidisciplinary effort to investigate and develop novel defensin analogues involving computer modeling, biochemistry, proteomics, chemical synthesis, molecular biology and clinical sciences.Oncology in SingaporeStünkel et al., Biotechnol. J. 2007, 2, 1360–1368Targeting apoptotic pathways using specific inhibitors has emerged as a valuable new approach in the treatment of cancer, which may decrease cytotoxicity and therefore side effects due to specificity for tumor cells. The NAD+‐dependent protein deacetylase SIRT1 is linked to cellular survival pathways by virtue of keeping the tumor suppressor gene p53 and members of the forkhead transcription factor family deacetylated. To validate SIRT1 as a therapeutic anti‐cancer target, Walter Stünkel and other researchers from Singapore study the in vivo expression of SIRT1 in cancer specimens. They conclude that it may not be sufficient to block the catalytic function of SIRT1, and that its survival effects may be mainly brought about by means other than the deacetylase function. The increased cytosolic expression of SIRT1 in cancer cells could be an indicator of such novel functions.