Biomedical subjects

B Fischer

Publications and source records attributed to B Fischer.

At least 91 records · Page 5Linked to original sources

PubMed2000

Generation of antibodies directed against the low-immunogenic peptide-toxins microcystin-LR/RR and nodularin.

The preparation of antibodies against the liver toxin microcystin, as described here, is of major importance for its detection and purification in food and water, and for a therapeutic approach to neutralize the toxin by passive immunization. Microcystin-LR (MLR) and microcystin-RR (MRR) were purified from cyanobacterial cell materials by extraction, Sephadex LH-20-, ODS silica gel-, ionic exchange and RP-HPLC-chromatography. In order to reduce the toxicity for parenteral administration, microcystins were coupled by the carbodiimide method to poly-L-lysine (PLL(50.000)). Mice and rabbits were immunized with the conjugates in the presence of two lipopeptide immunoadjuvants (P(3)CSK(4) and P(3)CS-T(h)). High MLR-specific antibody levels were observed after parenteral coadministration of antigen and lipopeptides, whereas no anti-MLR antibodies were obtained with free microcystin or the microcystin-PLL(50.000)-conjugate in the absence of lipopeptide. In oral immunization, coadministration of antigen and adjuvants resulted in an accelerated development of anti MLR-specific antibodies and high antibody levels. Using the antisera, we could detect different microcystins and nodularin down to a concentration range of 10-50 ng/ml by a competitive inhibition ELISA; detection of microcystins in crude cell preparations was also possible. Furthermore, microcystins from different sources could be detected and discriminated from cyclic cyanopeptolines.

Administration, Oral↗

PubMed2000

T cell activation by recombinant FcepsilonRI gamma-chain immune receptors: an extracellular spacer domain impairs antigen-dependent T cell activation but not antigen recognition.

T cells can be endowed with antigen specificity by grafting with a chimeric receptor consisting of an extracellular antigen binding moiety (scFv) derived from an antibody and an intracellular signaling domain. Conflicting data exist on the impact of an extracellular spacer domain between the antigen binding and the signaling domain with respect to cellular activation. Here, we recorded conjugate formation and antigen-driven cellular activation of T cells grafted with receptor molecules that contain the same antigen binding site (anti-CD30 HRS3-scFv) and signaling domain (FcepsilonRI gamma-chain), however, with and without an IgG1 CH2CH3 (Fc) spacer domain between the scFv and transmembrane moiety. Receptors of both configurations mediate equally efficient conjugate formation between receptor grafted T cells and antigen-positive target cells. Specific signaling by the spacer containing receptor, however, is blocked by five- to 10-fold lower concentrations of soluble antigen than by the spacer-less receptor indicating a higher avidity of the spacer containing receptor to soluble antigen. In contrast, cellular activation upon binding to antigen-positive cells is mediated more efficiently by the spacer-less receptor. This demonstrates that the extracellular spacer domain impairs antigen-dependent cellular activation by the chimeric immune receptor, but not intercellular conjugate formation.

Animals↗

PubMed2000

An acidic microenvironment impairs the generation of non-major histocompatibility complex-restricted killer cells.

The microenvironment within solid tumours has often been shown to exhibit an acidic local pH. In recent studies we could demonstrate that an acidic extracellular pH (pHe) inhibits the non-major histocompatibility complex (MHC) -restricted cytotoxicity of immunocompetent effector cells. However, within tumours the activation of cytotoxic cells may already be impaired by low pHe. Therefore, we investigated the influence of acidic conditions on the generation of active killer cells. The cytotoxic activity of natural killer (NK) as well as lymphokine-activated killer (LAK) cells against K562, Daudi and Raji cells was analysed after an activation period of 3 days at pHe 7.2-6.5. A minor reduction of pHe from 7.2 to 7.0 during the culture period resulted in a strong inhibition of the natural cytotoxicity of NK cells. Furthermore, acidic pHe below 7.2 prevented the generation of activated LAK cells by interleukin-2 (IL-2). The cytotoxic capacity could not be reconstituted if cells cultured at a pHe of 6.5 were returned to physiological pH for another 24 hr. Analysis of the cellular subtypes within the various cultures did not reveal differences regarding the frequencies of NK cells, CD8+ T cells, or CD4+ T cells. However, an acidic pHe clearly inhibited the activation-induced increase of relevant adhesion molecules. The production of cytokines which are involved in the regulation of the cytotoxic process (tumour necrosis factor-alpha, interferon-gamma, IL-10, IL-12 and transforming growth factor-beta1) was also affected by pHe, as their release was strongly inhibited at pHe 7.0. Furthermore, we observed a considerable decrease in the metabolic activity of effector cells at acidic pHe. In summary, our findings suggest that an acidic microenvironment impairs the induction of an anti-tumoral immune response within solid tumours.

CD4-Positive T-Lymphocytes↗

PubMed2000

Receptor-mediated effects of chlorinated hydrocarbons.

This short review summarizes some recent findings on arylhydrocarbon (dioxin) receptor expression during early pregnancy in mammals. The arylhydrocarbon receptor is a ligand-activated transcription factor and was originally described as a mediator of the toxic effects of dioxins and other chlorinated hydrocarbons such as polychlorinated biphenyls. Orally administered polychlorinated biphenyls accumulate in uterine secretions, in the pre-implantation blastocyst, in the foetus and in the placenta. Coplanar polychlorinated biphenyls are known ligands of the arylhydrocarbon receptor. Deletion experiments indicate physiological roles of the arylhydrocarbon receptor during development and for the function of various organs. During early pregnancy, the arylhydrocarbon receptor is specifically expressed in pre-implantation embryos, during blastocyst differentiation and implantation, in the endometrial epithelium and in the decidua cells of the placenta. Coplanar polychlorinated biphenyls were found to be embryotoxic in low doses, i.e. in doses found in tissues of not specifically exposed individuals originating from xenobiotic environmental background contamination. In initial experiments, low-dose exposure of rabbit blastocysts to coplanar polychlorinated biphenyls in vitro did not induce transcriptional changes of the so-called arylhydrocarbon receptor gene battery. The embryological and toxicological implications of the findings are discussed.

Animals↗

PubMed2000

Voluntary saccadic control in dyslexia.

The role of eye-movement control in dyslexia is still unclear. Recent studies, however, confirmed that dyslexics show poor saccadic control in single and sequential target tasks. In the present study we investigated whether dyslexic subjects are impaired on an antisaccade task requiring saccades against the direction of a stimulus. Altogether, 620 subjects between the ages of 7 and 17 years were classified as dyslexics (N = 506) or control subjects (N = 114) on the grounds of the discrepancy between their intellectual abilities and reading/spelling achievements. All subjects performed an overlap prosaccade and a gap antisaccade task with 100 trials to each side of stimulation in random order. Variables analysed were the overall saccadic reaction time of both tasks; and from the antisaccade task the number of errors (prosaccades), the number of corrected errors, and the number of trials in which the subjects still failed to reach the side opposite the stimulus even after two saccades. An analysis of variance was carried out taking into account the development of saccadic behaviour with age and the differences between the groups. The results confirm development of saccade control with age, especially in the voluntary component (a frontal-lobe function) for both groups, but indicate that the antisaccade task performance, as measured by the error and the correction rate, is significantly worse in the dyslexic group at ages above 8 years. Up to 50% of the dyslexics performed the antisaccade task 1.5 standard deviations below the mean of the controls.

Adolescent↗

PubMed2000

Dynamic visual perception of dyslexic children.

This study describes the capacity of children to detect fast changes of a small visual pattern. Three visual detection tasks for a group of normally reading (N = 140) and another group of dyslexic children (N = 366) in the age range of 7 to 16 years have been used. All three tasks require the detection of the fast changing orientation of a small pattern before it disappears. In one task, stationary fixation was required, because the orientation changes took place always at the same location. In the saccade condition, the pattern was displaced suddenly to one or the other side and a saccade was required to detect the orientation. In a third condition, a distractor was presented at one side shortly before the oriented pattern appeared at the opposite side. In this case, an antisaccade with respect to the distractor was required. In all three conditions, the dyslexic group as a whole performed significantly below the level of the control group. The performance improved with age in both groups. The differences between the test and control group were largest in the distractor condition. When compared with eye-movement performance in an antisaccade task, a parallel development of the performance of both tasks was observed in both groups. The study shows that a certain percentage of dyslexic children has difficulties in the perception of fast changing stimuli, a task presumably challenging the magnocellular system.

Adolescent↗

PubMed2000

Effects of visual training on saccade control in dyslexia.

This study reports the effects of daily practice of three visual tasks on the saccadic performance of 85 dyslexic children in the age range of 8 to 15 years. The children were selected from among other dyslexics because they showed deficits in their eye-movement control, especially in fixation stability and/or voluntary saccade control. Their eye movements were measured in an overlap prosaccade and a gap antisaccade task before and after the training. The three tasks used for the training included a fixation, a saccade, and a distractor condition. In any of these tasks, the subject had to detect the last orientation of a small pattern which rapidly changed its orientation between up, down, right, and left, before it disappeared after some time. The task was to press one of four keys corresponding to the last orientation. The visual pattern was presented on an LCD display of a small hand-held instrument given to the children for daily use at home. The results indicate that daily practice improved not only the perceptual capacity, but also the voluntary saccade control, within 3 to 8 weeks. After the training, the group of dyslexics was no longer statistically different from the control group.

Adolescent↗

PubMed2000

Delayed and blunted induction of mRNA for tissue plasminogen activator in the brain of old rats following pentylenetetrazole-induced seizure activity.

The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. Here we investigated the extent to which old rats retain the capacity to initiate transcription for immediate early genes, particularly as it relates to brain plasticity, in response to a strong stimulus. The intraperitoneal administration of pentylenetetrazole (PTZ) to rats of various ages evoked tonic-clonic seizures. Using an RNA gel-blot and in situ hybridization analysis, we found that 1 hour after the onset of seizure, messenger RNA (mRNA) for tissue plasminogen activator (TPA) was increased approximately 3.7-fold in the hippocampi of 3-month-old rats. The levels of TPA mRNA in the hippocampi and cortices of 3-month-old rats returned to control levels by 3 hours after PTZ administration. The levels of TPA mRNA increased 2.5-fold in the hippocampi of 18-month-old rats and 1.8-fold in the brains of the 28-month-old-rats at 3 hours and returned to basal levels by 15 hours following PTZ treatment. Quantitatively similar increases were calculated for the cortex. At peak induction the transcripts were localized throughout the cortical layers of the 3-month-old rats, whereas the TPA mRNA expression was restricted to cortical layer V of the older rats. Our results suggest that although the aging brain retains the capacity to respond to chemically induced seizures, the induction of TPA mRNA is temporarily delayed and the levels are diminished with increasing age. Because TPA has been implicated in neuronal plasticity, this finding suggests that immediate early genes are important factors in the limited plasticity of the aging brain.

Aging↗

PubMed2000

Oxygen stress increases prolyl cis/trans isomerase activity and expression of cyclophilin 18 in rabbit blastocysts.

The peptidyl-prolyl cis/trans isomerase (PPIase) activity and the expression of cyclophilins were studied in 6-day-old rabbit preimplantation embryos cultured under physiological and increased oxygen concentrations of 5% and 20% O(2), respectively. The PPIase activity was completely inhibited by cyclosporin A (CsA). The inhibitor of FK506-binding proteins, rapamycin, had no effect on the PPIase activity, indicating that the PPIase activity in rabbit blastocysts originates from cyclophilins. Using CsA affinity chromatography, only one cyclophilin with a molecular mass of about 17.8 kDa was separated. The cDNA of rabbit cyclophilin was cloned and sequenced. Analysis of the 682-base pair cDNA revealed an open reading frame coding for a polypeptide of 164 amino acid residues with a molecular weight of 17.83 kDa. Homologies of 90% and 96% for the cDNA and amino acid sequence, respectively, to the human CyP18 were found, suggesting that the novel rabbit cyclophilin is a member of the CyP18 family (rabCyP18). The transcription level of rabCyP18 mRNA was 8.3 +/- 0.6 pg in 100 ng total RNA in noncultured blastocysts. In vitro culture with moderate oxygen stress (20% O(2)) resulted in a 1.5-fold increase in rabCyP18 transcription and an increased PPIase activity compared to that of blastocysts cultured with 5% O(2). Increase in transcription rate and PPIase activity by oxygen stress suggests an involvement of CyP18 in oxygen defense in rabbit preimplantation embryos.

Amino Acid Sequence↗

PubMed2000

Ruminant relaxin in the pregnant one-humped camel (Camelus dromedarius).

We have determined the cDNA sequence of preprorelaxin in the pregnant one-humped camel by employing reverse transcription- and rapid amplification of cDNA ends-polymerase chain reaction. Camel preprorelaxin consisted of 600 base pairs (bp) encoding a protein of 199 amino acids (aa) with a signal peptide of 25 aa (75 bp), a B domain of 28 aa (84 bp), a C domain of 121 aa (366 bp), and an A domain of 24 aa (72 bp). The N terminus of the C domain of camel prorelaxin contained the unique proline-rich repetitive sequence (-RPAP)(3)-(-K/RPAL-)(2), and within the B domain the classical -GRELVR- receptor binding motif was found. Camel preprorelaxin showed highest homology with porcine (74.6%) and equine (65.4%) relaxin. The ovary and the uteroplacental unit were a dual source of relaxin in the pregnant dromedary. Within the ovary, weak expression of relaxin was detected in large luteal cells of the mature corpus luteum. In the ovarian follicles, immunoreactive relaxin, but not relaxin mRNA, was detected in the granulosa and theca interna cell layer. Beginning at around Day 93 of gestation and coinciding with increasing interdigitation of the fetal villus with the underlying maternal endometrium, uterine luminal epithelial cells in the uteroplacental tissue expressed relaxin. Weak expression of immunoreactive relaxin, but not relaxin mRNA, was observed in villous trophoblast cells. Pseudostratified trophoblast cells at the base of the placental villi and multinucleate giant cells did not express relaxin.

Amino Acid Sequence↗

PubMed2000

Experimental observation of localization in the spatial frequency domain of a kicked optical system

An experimental realization of an optical "kicked" system is presented. It exhibits localization analogous to that of the quantum "kicked-rotor." In the experiment, free space propagating light is periodically kicked by thin sinusoidal phase gratings, which produce high order diffractions and tend to increase the spatial frequency band. The wave property suppresses this diffusive spread. The localization is realized in a regime near anti-resonance of the system, which is also studied theoretically. The behavior in this regime is similar to that of electronic motion in incommensurate potentials. A crucial part of the experimental system is the grating in-phase positioning, which is done by using the Talbot effect.

Journal Article↗

PubMed2000

Trophoblast cell-specific carcinoembryonic antigen cell adhesion molecule 9 is not required for placental development or a positive outcome of allotypic pregnancies.

The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily divergent glycoproteins. The secreted pregnancy-specific glycoproteins constitute a subgroup within the CEA family. They are predominantly expressed in trophoblast cells throughout placental development and are essential for a positive outcome of pregnancy, possibly by protecting the semiallotypic fetus from the maternal immune system. The murine CEA gene family member CEA cell adhesion molecule 9 (Ceacam9) also exhibits a trophoblast-specific expression pattern. However, its mRNA is found only in certain populations of trophoblast giant cells during early stages of placental development. It is exceptionally well conserved in the rat (over 90% identity on the amino acid level) but is absent from humans. To determine its role during murine development, Ceacam9 was inactivated by homologous recombination. Ceacam9(-/-) mice on both BALB/c and 129/Sv backgrounds developed indistinguishably from heterozygous or wild-type littermates with respect to sex ratio, weight gain, and fertility. Furthermore, the placental morphology and the expression pattern of trophoblast marker genes in the placentae of Ceacam9(-/-) females exhibited no differences. Both backcross analyses and transfer of BALB/c Ceacam9(-/-) blastocysts into pseudopregnant C57BL/6 foster mothers indicated that Ceacam9 is not needed for the protection of the embryo in a semiallogeneic or allogeneic situation. Taken together, Ceacam9 is dispensable for murine placental and embryonic development despite being highly conserved within rodents.

Animals↗

PubMed2000

Neutrophil elastase induces MUC5AC messenger RNA expression by an oxidant-dependent mechanism.

Airway diseases such as cystic fibrosis, chronic bronchitis, and viral- or pollution-triggered asthma have two common pathologic features: mucus obstruction of the airways, and neutrophil-predominant airway inflammation. Neutrophils release high concentrations of elastase (neutrophil elastase [NE]), a serine protease, into the airways; exposure to elastase results in secretory metaplasia and increased production/secretion of mucin glycoproteins. We have previously shown that NE increases gene expression of a respiratory mucin, MUC5AC, in both A549, a lung adenocarcinoma cell line, and cultured normal human bronchial epithelial cells. In this study, we explored the intracellular signaling mechanisms required for NE-regulated MUC5AC gene expression. A549 cells were treated with dimethylthiourea (DMTU; 4 mM and 40 mM), a scavenger of hydroxyl radical, peroxynitrite, and other hydroxylated products, prior to and during NE stimulation. DMTU inhibited NE-induced MUC5AC expression. Furthermore, using dichlorodihydrofluorescein, an intracellular redox indicator, we showed that in both A549 cells and cultured normal human bronchial epithelial cells, NE treatment induced oxidative stress. These results support the role of reactive oxygen species mediating NE-induced MUC5AC gene expression.

Blotting, Northern↗

PubMed2000

Prescriptions, power and politics: the turbulent history of methadone maintenance in Canada.

Illicit opiate addiction has emerged as a major problem in many Western countries in the second half of this century, and its social harm implications have become much exacerbated with the onset of the HIV epidemic in the 1980s. By now, most Western jurisdictions have resorted to methadone treatment as the most effective and best researched intervention against the negative consequences of opiate addiction including mortality, morbidity, crime, and loss of social functioning. Methadone treatment in Canada features a long, turbulent, and instructive history as an exemplary case study in public policy. While both Britain and the U.S. experimented with opiate prescription treatment in the first half of the century, Canadian proposals for such programs initially never made it beyond the discussion stage, largely due to the influential resistance from the law enforcement sector. However, in light of growing influence from an emerging addictions treatment sector, Canada became the first Western jurisdiction to experiment with methadone prescription for the treatment of opiate addiction forty years ago. Methadone treatment became quickly and widely established as an effective treatment modality through the 1960s. But in the early 1970s, resistance from the law and health sectors evolved, and triggered the government to establish a set of comprehensive and restrictive federal methadone treatment regulations, which have dominated its realities until today. Almost completely regulated out of existence by the end of the 1970s, methadone treatment's prevalence gradually increased again through the 1980s, and recent decentralization efforts to provincial levels earlier this decade have had dramatic effects on treatment availability. Significant events in the Canadian history of methadone treatment and its regulation reflect developments in the U.S., and substantial recent domestic treatment expansion developments--as well as renewed sparks of resistance--are reminiscent of methadone treatment's patterns of history as they developed in the late 1960s. This paper traces the turbulent history of methadone treatment, regulation and policy in Canada with particular attention to institutional, professional and political determinants at the complex intersection of health, law, and addiction.

Canada↗

PubMed2000

2-Thioether-5'-O-(1-thiotriphosphate)-adenosine derivatives: new insulin secretagogues acting through P2Y-receptors.

P2-receptors (P2-Rs) represent significant targets for novel drug development. P2-Rs were identified also on pancreatic B cells and are involved in insulin secretion. The aim of our study was to synthesize and evaluate pharmacologically the novel P2Y-R ligands, 2-thioether-5'-O-phosphorothioate adenosine derivatives, as potential insulin secretagogues. An efficient synthesis of these nucleosides and a facile method for separation of the chiral products is described. The enzymatic stability of the compounds towards pig-pancreas NTPDase was evaluated. The rate of hydrolysis of 2-hexylthio-5'-O-(1-thiotriphosphate)-adenosine (2-hexylthio-ATP-alpha-S) isomers by NTPDase was 28% that of ATP. The apparent affinity of the compounds to P2Y1-R was determined by measurement of P2Y-receptor-promoted phospholipase C activity in turkey erythrocyte membranes. 2-RS-ATP-alpha-S derivatives were agonists, stimulating the production of inositol phosphates with K0.5 values in the nM range. 2-RS-AMP-S derivatives were full agonists although 2 orders of magnitude less potent. All the compounds were more potent than ATP. The effect on insulin secretion and pancreatic flow rate was evaluated on isolated and perfused rat pancreas. A high increase, up to 500%, in glucose-induced insulin secretion was due to addition of 2-hexylthio-ATP-alpha-S in the nM concentration range, which represents 100-fold enhancement of activity relative to ATP. 2-Hexylthio-AMP-S was 2.5 orders of magnitude less effective. A high chemical hydrolytic stability was observed for 2-hexylthio-ATP-alpha-S. Hydrolysis of the phosphoester bond, which was the only detectable degrading reaction under the investigation conditions (pH 7.4, 37 degrees C), was slow, with a half-life of 264 hours. Moreover, even at gastric juice conditions (pH 1.4, 37 degrees C), hydrolysis of the terminal phosphate was the only detectable reaction, with a half-life of 17.5 hours. 2-Hexylthio-ATP-alpha-S isomers are enzymatically and chemically stable. These isomers are highly potent and effective insulin secretagogues, increasing, however, pancreatic vascular resistance.

Acid Anhydride Hydrolases↗

PubMed2000

Stability of gaze control in dyslexia.

The neurobiological basis of saccade control has at least three components: fixation, reflexes, voluntary control. It was found in earlier studies that the voluntary component of saccade is specifically impaired in dyslexics as compared with controls of the same age. In this study, we searched for evidence of fixation instability by analyzing the eye movements of 99 control subjects and 262 dyslexics (age 7-17 years) performing an overlap prosaccade and a gap antisaccade task. The percentage of intrusive saccades was counted for each subject during a period of the trial where stationary fixation was required. Both groups showed improvements of fixation stability with age, but the dyslexic group exhibited developmental deficits. It is discussed whether these deficits could be interpreted as consequences of deficits in the magnocellular pathway.

Adolescent↗

PubMed1999

Molecular recognition of modified adenine nucleotides by the P2Y(1)-receptor. 1. A synthetic, biochemical, and NMR approach.

The remarkably high potencies of 2-thioether-adenine nucleotides regarding the activation of the P2Y(1)-receptor (P2Y(1)-R) in turkey erythrocyte membranes represent some of the largest substitution-promoted increases in potencies over that of a natural receptor ligand. This paper describes the investigation regarding the origin of the high potency of these P2Y(1)-R ligands over that of ATP. For this study, an integrated approach was employed combining the synthesis of new ATP analogues, their biochemical evaluation, and their SAR analysis involving NMR experiments and theoretical calculations. These experiments and calculations were performed to elucidate the conformation and to evaluate the electronic nature of the investigated P2Y(1)-R ligands. ATP analogues synthesized included derivatives where C2 or C8 positions were substituted with electron-donating groups such as ethers, thioethers, or amines. The compounds were tested for their potency to induce P2Y(1)-R-mediated activation of phospholipase C in turkey erythrocytes and Ca(2+) response in rat astrocytes. 8-Substituted ATP and AMP derivatives had little or no effect on phospholipase C or on calcium levels, whereas the corresponding 2-substituted ATP analogues potently increased the levels of inositol phosphates and ¿Ca(2+)(i). AMP analogues were ineffective except for 2-butylthio-AMP which induced a small Ca(2+) response. P2Y(1)-R activity of these compounds was demonstrated by testing these ligands also on NG108-15 neuroblastoma x glioma hybrid cells. NMR data together with theoretical calculations imply that steric, rather than electronic, effects play a major role in ligand binding to the P2Y(1)-R. Hydrophobic interactions and H-bonds of the C2 substituent appear to be important determinants of a P2Y(1)-R ligand affinity.

Adenine Nucleotides↗

PubMed1999

Molecular recognition of modified adenine nucleotides by the P2Y(1)-receptor. 2. A computational approach.

The molecular recognition of C2- or C8-substituted ATP derivatives by the P2Y(1)-receptor (P2Y(1)-R) is analyzed using ab initio quantum mechanical calculations. Parameters that may determine ligand specificity toward P2Y(1)-R were examined on reduced models and correlated with the biochemical data for the parent compounds. These include tautomerism and protonation energy in the gas and aqueous phases, as well as molecular electrostatic potential (MEP) and dipole moment vector. The calculated electronic parameters cannot explain the inactivity of the C8-substituted ATP derivatives, nor the difference in activity among the C2-substituted ATP analogues. These results indicate that neither tautomerism nor changes in the electronic distribution of the adenine ring play a major role in determining binding specificity of adenine nucleotides to the receptor. It is suggested that the higher potency of the C2-substituted ATP derivatives, compared to ATP, might be due to interaction between the C2 side chain heteroatom and the receptor. Furthermore, the interaction of the C2 alkyl side chain with a hydrophobic pocket at the receptor binding site is suggested. In addition, NMR data in the companion paper indicate that the inactivity of the C8-substituted ATP analogues may be due to steric and conformational, rather than electronic, effects.

Adenine Nucleotides↗