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Real time kinetic studies were used to map conformational epitopes in human chorionic gonadotropin (hCG) for two monoclonal
antibodies (MAbs). The epitopes were identified in the regions (α5-14 and α55-62). The association rate constant (k+1) was found to be altered by chemical modification of hCG, and the ionic strength of the reaction medium. Based on these changes,
we propose the presence of additional interactions away from the epitope-paratope region in the hCG-MAb reaction. We have
identified such incidental interacting regions (IIRs) in hCG to be the loop region α35-47 and α60-84. The IIRs contribute
significantly towards theK
A of the interaction. Therefore, in a macromolecular interaction of hCG and its MAb,K
A is determined not only by epitopeparatope interaction but also by the interaction of the nonepitopic-nonparatopic IIRs. However,
the specificity of the interaction resides exclusively with the epitope-paratope pair. 相似文献
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Putluri N Shojaie A Vasu VT Nalluri S Vareed SK Putluri V Vivekanandan-Giri A Byun J Pennathur S Sana TR Fischer SM Palapattu GS Creighton CJ Michailidis G Sreekumar A 《PloS one》2011,6(7):e21417
Prostate cancer is the second leading cause of cancer related death in American men. Development and progression of clinically localized prostate cancer is highly dependent on androgen signaling. Metastatic tumors are initially responsive to anti-androgen therapy, however become resistant to this regimen upon progression. Genomic and proteomic studies have implicated a role for androgen in regulating metabolic processes in prostate cancer. However, there have been no metabolomic profiling studies conducted thus far that have examined androgen-regulated biochemical processes in prostate cancer. Here, we have used unbiased metabolomic profiling coupled with enrichment-based bioprocess mapping to obtain insights into the biochemical alterations mediated by androgen in prostate cancer cell lines. Our findings indicate that androgen exposure results in elevation of amino acid metabolism and alteration of methylation potential in prostate cancer cells. Further, metabolic phenotyping studies confirm higher flux through pathways associated with amino acid metabolism in prostate cancer cells treated with androgen. These findings provide insight into the potential biochemical processes regulated by androgen signaling in prostate cancer. Clinically, if validated, these pathways could be exploited to develop therapeutic strategies that supplement current androgen ablative treatments while the observed androgen-regulated metabolic signatures could be employed as biomarkers that presage the development of castrate-resistant prostate cancer. 相似文献
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Srilatha Simhadri Shaun Peterson Dharm S. Patel Yanying Huo Hong Cai Christian Bowman-Colin Shoreh Miller Thomas Ludwig Shridar Ganesan Mantu Bhaumik Samuel F. Bunting Maria Jasin Bing Xia 《The Journal of biological chemistry》2014,289(35):24617-24629
PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis. 相似文献
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A bicistronic vector with destabilized mRNA secondary structure yields scalable higher titer expression of human neurturin in E. coli
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Huy Dao Prit Lakhani Anitha Police Venkataraman Kallakunta Sankar Srinivas Ajjarapu Kai-Wei Wu Pranav Ponkshe Michael A. Repka S. Narasimha Murthy 《AAPS PharmSciTech》2018,19(1):60-78
This review gives a brief overview about microbial contamination in pharmaceutical products. We discuss the distribution and potential sources of microorganisms in different areas, ranging from manufacturing sites, pharmacy stores, hospitals, to the post-market phase. We also discuss the factors that affect microbial contamination in popular dosage forms (e.g., tablets, sterile products, cosmetics). When these products are contaminated, the microorganisms can cause changes. The effects range from mild changes (e.g., discoloration, texture alteration) to severe effects (e.g., changes in activities, toxicity). The most common method for countering microbial contamination is the use of preservatives. We review some frequently used preservatives, and we describe the mechanisms by which microorganisms develop resistance to these preservatives. Finally, because preservatives are inherently toxic, we review the efforts of researchers to utilize water activity and other non-preservative approaches to combat microbial contamination. 相似文献
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Cole AG Stroke IL Brescia MR Simhadri S Zhang JJ Hussain Z Snider M Haskell C Ribeiro S Appell KC Henderson I Webb ML 《Bioorganic & medicinal chemistry letters》2006,16(1):200-203
The identification and evaluation of aryl-[1,4]diazepane ureas as functional antagonists of the chemokine receptor CXCR3 are described. Specific examples exhibit IC(50) values of approximately 60 nM in a calcium mobilization functional assay, and dose-dependently inhibit CXCR3 functional response to CXCL11 (interferon-inducible T-cell alpha chemoattractant/I-TAC) as measured by T-cell chemotaxis, with a potency of approximately 100 nM. 相似文献
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