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1.
Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
2.
Surface plasmon resonance (SPR) analysis was used to assess the immunoreactivity of anti-biotin (4) and anti-fluorescein (5) monoclonal antibody after conjugation with the N-hydroxysuccinimide ester of acridinium-9-carboxamide 1. Only minor changes in the apparent equilibrium dissociation constants of the antibody conjugates for their ligands resulted from the conjugation process. However, comparison of the initial binding rate of the conjugates with their ligands with those of the unmodified antibodies over a range of concentrations showed that the antibody conjugates were partially inactivated. The anti-fluorescein conjugates retained at least 90% of their immunoreactivity over the range of modification tested, while anti-biotin conjugates showed a progressive loss of reactivity with increased substitution by the label. 相似文献
3.
Adamczyk M Chen YY Fishpaugh JR Mattingly PG Pan Y Shreder K Yu Z 《Bioconjugate chemistry》2000,11(5):714-724
Four chemiluminescent N-sulfonylacridinium-9-carboxamide active esters (17-20) were prepared from the corresponding acids and coupled to both of the aminated phenobarbital (13) and N-(6-aminohexyl)phenytoin (16) haptens. The level of signal produced by chemiluminescent N-sulfonylacridinium-9-carboxamide phenobarbital and phenytoin tracers in a solid-phase immunoassay format was found to be modulated by at least 20-fold by the judicious choice of the reactive acridinium-hapten linking group. 相似文献
4.
Shreder KR Wong MS Corral S Yu Z Winn DT Wu M Hu Y Nomanbhoy T Alemayehu S Fuller SR Rosenblum JS Kozarich JW 《Bioorganic & medicinal chemistry letters》2005,15(19):4256-4260
Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM. 相似文献
5.
Shreder K 《Methods (San Diego, Calif.)》2000,20(3):372-379
The molecular forces that bind antibody to antigen have long fascinated chemists. The use of synthetic haptens to study immunochemical phenomena can be traced back to the classic work of Karl Lansteiner. His utilization of small-molecule-protein conjugates first demonstrated the shape-selective nature of antibody binding. Later work by Linus Pauling and David Pressman employed multivalent, synthetic ligands to establish the bivalent nature of antibodies and explain the nature of immunoprecipitation. Fluorescent probes such as dansyl, fluorescein, and Ru(bpy)(2+)(3) have been used to study affinity maturation, quantify antibody affinities, and investigate polyclonal antibody heterogeneity. Finally, X-ray crystallography has yielded a molecular picture of how antibodies exercise intermolecular forces (e.g., charge-charge interactions, H-bonding, and Van der Waals) to bind haptens. Studies inspired by Landsteiner's original work continue to play an important role in fields ranging from immunodiagnostics to catalytic antibodies. 相似文献
6.
KR Rupesh PL PremKumar Vasanth V Shiva Kumar Seetharaman S Jayachandran 《BMC microbiology》2002,2(1):5-7
Background
Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP. 相似文献7.
8.
A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions. 相似文献
9.
Regeneration and reestablishment of synaptic connections is an important topic in neurobiological research. In the present study, the regeneration of auditory afferents and the accompanying effects in the central nervous system are investigated in nymphs and adults of the bush cricket Tettigonia viridissima L. (Orthoptera: Tettigoniidae). In all animals in which the tympanal nerve is crushed, neuronal tracing shows a regrowth of the afferents into the prothoracic ganglion. This regeneration is seen in both adult and nymphal stages and starts 10–15 days after nerve crushing. Physiological recordings from the leg nerve indicate a recovery of tympanal fibres and a formation of functional connections to interneurones in the same time range. Electrophysiological recordings from the neck connective suggest additional contralateral sprouting of interneurones and the formation of aberrant connections. The regeneration processes of the tympanal nerve in nymphal stages and adults appear to be similar. 相似文献
10.
Li B Cociorva OM Nomanbhoy T Li Q Nakamura K Nomura M Okada K Yumoto K Liyanage M Zhang MC Aban A Szardenings AK Kozarich JW Kohno Y Shreder KR 《Bioorganic & medicinal chemistry letters》2012,22(2):1005-1008
We previously disclosed tricylic, 6-carboxylic acid-bearing 4-quinolones as GSK-3β inhibitors. Herein we discuss the optimization of this series to yield a series of more potent 6-nitrile analogs with insignificant anti-microbial activity. Finally, kinase profiling indicated that members of this class were highly specific GSK-3 inhibitors. 相似文献