Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drugtarget specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer's disease (AD). Secondary and tertiary protein structure predictions followed by proteinprotein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD.
BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) R132 mutations occur as point mutations at a frequency of 70% or more in gliomas, including astrocytoma and oligodendroglioma, of WHO grades 2 and 3, as well as secondary glioblastoma. Because this gene abnormality is not observed in normal cells or non-glioma brain tumors, the diagnosis of glioma is nearly certain if an IDH1 mutation is detected. We established a high-resolution melting analysis method that uses single nucleotide polymorphism analysis based on real-time PCR and that reliably and quickly detect IDH1 mutations. Further, we attempted to apply it in rapid diagnosis during glioma surgery. METHODS: DNA extracted in 15 min from neoplastic tissue collected during surgery was used to test for R132 point mutations of the IDH1 gene by using real-time PCR/high resolution melting analysis method. Normally, detecting IDH1 mutations requires about 80 min from the start of the PCR cycle. For rapid diagnosis, however, DNA extension and annealing times in the PCR cycle were reduced by half. Our results were compared with those obtained using the regular method. RESULTS: Regular analysis and rapid diagnosis analysis were used to detect IDH1 mutations in 6 glioma cases (diffuse astrocytoma, 2 cases; oligodendroglioma, 2 cases; anaplastic astrocytoma, 1 case; glioblastoma, 1 case). Both methods produced the same results in all cases. CONCLUSION: Direct DNA sequencing and immunostaining can be used to identify IDH1 mutations. However, because analyses by using the former method require several hours. The latter method could not identify all R132 mutations, because the current commercially available antibodies can only detect R132H mutant proteins. Our method can determine all IDH1 R132 mutation-positive gliomas during surgery in 50 -60 min after the tissue is collected. Further, this method could aid in intraoperative pathological diagnoses to differentiate IDH1 mutation-positive low-malignancy gliomas from gliosis and other non-neoplastic tissues. PA-002. CNS LYMPHOMAS: GEOGRAPHICAL VARIATIONS AND EFFECT OF STEROIDS ON HISTOLOGICAL DIAGNOSISArivazhagan Arimappamagan, N Manoj, Anita Mahadevan, DI Bhat, HR Arvinda, B Indiradevi, Sampath Somanna, and BA Chandramouli; National Institute of Mental Health and Neurosciences, Bangalore, India BACKGROUND: CNS lymphomas in Indian population are known to differ in epidemiology and clinical presentation from Western population. The duration of steroid intake which can affect the yield of stereotactic biopsy in lymphoma is not well established. AIMS: The present study analysed trends of hospital based incidence of PCNSL over two decades, relation to immune status in our settings and steroid effect on histology. METHODS: All cases of CNS lymphoma diagnosed in our institute from 1991 to 2010 were analysed retrospectively. The morphological phenotype (centroblastic/ immunoblastic) on routine stains and immunophenotype (B cell/T cell) were ascertained. RESULTS: 76 cases of primary CNS lymphoma were diagnosed in the study period. The hos...
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