Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, the gene encoding the cerebrovascular and neuritic plaque amyloid, a pathologic stigma of Alzheimer's disease (AD), has been molecularly cloned and mapped to human chromosome 21, band q21. Changes in the brains of individuals with trisomy 21 (Down syndrome, DS) over 35 years of age closely resemble AD neuropathology. Genetic homology which exists between human chromosome 21 (HSA 21) and mouse chromosome 16 (MMU 16) has led to the use of mice with trisomy 16 as a model system for studies relevant to DS. Mice with Ts16 exhibit numerous developmental abnormalities that can be correlated with features observed in DS, including neurochemical and neuroanatomic alterations. In this study, we show that the genetic homology between HSA 21 and MMU 16 extends to the gene encoding the amyloid peptide. The homologous mouse gene, designated Cvap, for cerebrovascular amyloid peptide, is localized on MMU 16 band C3----ter, and is in close proximity to both superoxide dismutase-1 (Sod-1), and the protooncogene, Ets-2, two of the genes known to localize to the DS region of HSA 21. Linkage of these genes has been maintained since the divergence of the common ancestor of mouse and man, despite a chromosomal rearrangement which has changed the gene order between the two species. These findings expand the region of HSA 21 with known homology to MMU 16, and provide a genetic basis to suggest that studies of the trisomy 16 mouse, in addition to being relevant to DS, may also clarify the role of abnormal gene expression in AD.
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PMID:Genetic linkage in the mouse of genes involved in Down syndrome and Alzheimer's disease in man. 296 Apr 20

Chrysamine G (CG), an analogue of Congo red, is known to bind in vitro to the beta-amyloid protein (Abeta 10-43) and to homogenates of several regions of the brain of Alzheimer's disease (AD) patients. We synthesised a conjugate of 2-(acetamido)-CG with a bis-S-trityl protected monoamide-monoaminedithiol (MAMA-Tr(2)) tetraligand, which was efficiently deprotected and labelled with a 75% yield with technetium-99m, to obtain (99m)Tc-MAMA-CG. In mice, (99m)Tc-MAMA-CG was cleared mainly by the hepatobiliary system, resulting in a fast blood clearance. Brain uptake of (99m)Tc-MAMA-CG was low. Co-injection with the blood pool tracer iodine-125 human serum albumin ((125)I-HSA) demonstrated a brain/blood activity ratio for (99m)Tc-MAMA-CG that was significantly higher than that for (125)I-HSA (t test for dependent samples, P<0.02), indicating the ability of (99m)Tc-MAMA-CG to cross the blood-brain barrier. In vitro autoradiography demonstrated pronounced binding of (99m)Tc-MAMA-CG to beta-amyloid deposits in autopsy sections of the parietal and occipital cortex of an AD patient as compared with controls. Adding 10 microM Congo red during incubation displaced the binding of (99m)Tc-MAMA-CG. Congo red staining and autoradiography identified the same lesions. (99m)Tc-MAMA-CG seems to bind selectively to beta-amyloid deposition in human brain parenchyma and blood vessels in vitro and thus might be a lead compound for further development of a useful tracer agent for the in vivo diagnosis of Alzheimer's disease.
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PMID:99mTc-MAMA-chrysamine G, a probe for beta-amyloid protein of Alzheimer's disease. 1055 79

The use of so-called protein scaffolds has recently attracted considerable attention in biochemistry in the context of generating novel types of ligand receptors for various applications in research and medicine. This development started with the notion that immunoglobulins owe their function to the composition of a conserved framework region and a spatially well-defined antigen-binding site made of peptide segments that are hypervariable both in sequence and in conformation. After the application of antibody engineering methods along with library techniques had resulted in first successes in the selection of functional antibody fragments, several laboratories began to exploit other types of protein architectures for the construction of practically useful binding proteins. Properties like small size of the receptor protein, stability and ease of production were the focus of this work. Hence, among others, single domains of antibodies or of the immunoglobulin superfamily, protease inhibitors, helix-bundle proteins, disulphide-knotted peptides and lipocalins were investigated. Recently, the scaffold concept has even been adopted for the construction of enzymes. However, it appears that not all kinds of polypeptide fold which may appear attractive for the engineering of loop regions at a first glance will indeed permit the construction of independent ligand-binding sites with high affinities and specificities. This review will therefore concentrate on the critical description of the structural properties of experimentally tested protein scaffolds and of the novel functions that have been achieved on their basis, rather than on the methodology of how to best select a particular mutant with a certain activity. An overview will be provided about the current approaches, and some emerging trends will be identified. (c) 2000 John Wiley & Sons, Ltd. Abbreviations used: ABD albumin-binding domain of protein G APPI Alzheimer's amyloid beta-protein precursor inhibitor BBP bilin-binding protein BPTI bovine (or basic) pancreatic trypsin inhibitor BSA bovine serum albumin CBD cellulose-binding domain of cellobiohydrolase I CD circular dichroism Cdk2 human cyclin-dependent kinase 2 CDR complementarity-determining region CTLA-4 human cytotoxic T-lymphocyte associated protein-4 FN3 fibronectin type III domain GSH glutathione GST glutathione S-transferase hIL-6 human interleukin-6 HSA human serum albumin IC(50) half-maximal inhibitory concentration Ig immunoglobulin IMAC immobilized metal affinity chromatography K(D) equilibrium constant of dissociation K(i) equilibrium dissociation constant of enzyme inhibitor LACI-D1 human lipoprotein-associated coagulation inhibitor pIII gene III minor coat protein from filamentous bacteriophage f1 PCR polymerase-chain reaction PDB Protein Data Bank PSTI human pancreatic secretory trypsin inhibitor RBP retinol-binding protein SPR surface plasmon resonance TrxA E. coli thioredoxin
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PMID:Engineered protein scaffolds for molecular recognition. 1093 55