Biomedical subjects

C H Lin

Publications and source records attributed to C H Lin.

At least 127 records · Page 7Linked to original sources

PubMed1999

The role of P wave in prediction of atrial fibrillation after coronary artery surgery.

Atrial fibrillation (AF) is a common arrhythmia after coronary artery bypass surgery (CABG). The purpose of this study was to determine the role of P wave duration, amplitude and dispersion in the prediction of AF after CABG. This study included 120 patients undergoing elective CABG. Clinical characteristics, 12-lead electrocardiogram (ECG), echocardiogram and coronary angiogram were obtained in all patients. We measured P wave duration, amplitude and dispersion from 12-lead ECG in each patient. After CABG, all patients were continuously monitored for AF attacks in the intensive care unit and ordinary ward. Our results showed that age greater than 60 years was the strongest predictor of postoperative AF (p<0.01), with a 3.7-fold greater likelihood of developing postoperative AF compared to ages less than 60 years. Gender was another independent predictor of postoperative AF, with men being 3.0 times more likely to develop postoperative AF compared to women (p = 0.03). The presence of prolonged P wave duration (> or =100 ms in lead II) was also an independent predictor (p = 0.04), with 2.9-fold greater risk of developing postoperative AF compared to a P wave duration of less than 100 ms. The P wave dispersion was similar between patients with and without postoperative AF (29+/-15 vs. 33+/-15 mm, p = NS). In conclusion, old age, male gender and prolonged P wave duration were independent predictors of AF after CABG. However, P wave dispersion and amplitude did not provide significant information in the prediction of postoperative AF.

Age Factors↗

PubMed1999

Heatstroke induces c-fos expression in the rat hypothalamus.

We induced heat stress in urethane-anesthetized rats (the animals were exposed to an ambient temperature at 42 degrees C), and monitored their colon temperature, mean arterial pressure and local cerebral blood flow. Rats 0, 20, 40 or 80 min after heat stress were sacrificed for determination of c-fos mRNA and protein expression in the paraventricular nucleus (PVN), supraoptic nucleus (SON) and preoptic nucleus (PON). The heatstroke, which appears as profound decreases in both mean arterial pressure and local cerebral blood flow and increases in colon temperature, is produced 80 min after heat stress. We show the c-fos mRNA and protein is strongly induced in all these nuclei of rat hypothalamus after the onset of heatstroke. We conclude that c-fos expression in the hypothalamus during rat heatstroke is associated with hyperthermia, arterial hypotension and cerebral ischemia.

Animals↗

PubMed1999

Overexpression of protein tyrosine phosphatase-alpha (PTP-alpha) but not PTP-kappa inhibits translocation of GLUT4 in rat adipose cells.

Protein tyrosine phosphatases (PTPases) are likely to play important roles in insulin action. We recently demonstrated that the nontransmembrane PTPase PTP1B can act as a negative modulator of insulin-stimulated translocation of GLUT4. We now examine the role of PTP-alpha and PTP-kappa (two transmembrane PTPases) in this metabolic action of insulin. Rat adipose cells were transfected with either PTP-alpha or PTP-kappa and effects of these PTPases on the translocation of a cotransfected epitope-tagged GLUT4 were studied. Cells overexpressing wild-type PTP-alpha had significantly lower levels of cell surface GLUT4 in response to insulin and a threefold decrease in insulin sensitivity when compared with control cells expressing only tagged GLUT4. Co-overexpression of PTP-alpha and PTP1B did not have additive effects, suggesting that these PTPases share common substrates. Cells overexpressing either wild-type PTP-kappa or catalytically inactive mutants of PTP-alpha had dose-response curves similar to those of control cells. Since overexpression of PTP-alpha, but not PTP-kappa, had effects on translocation of GLUT4, our data suggest that PTPalpha may be a specific negative modulator of insulin-stimulated glucose transport.

Adipocytes↗

PubMed1999

Kinetics of germanium dioxide in rats.

The kinetics of germanium dioxide (GeO2) in single dose and repeated exposures were investigated in male Wistar rats. In the single dose GeO2 (100 mg/kg BW, p.o.) exposure study, values of several kinetic parameters were shown as follows, a maximum concentration in serum of 15.5+/-0.7 microg/ml (mean +/- S.E.M.), an absorption half-life of 0.7+/-0.1 h (mean +/- S.E.M.), an elimination half-life of 2.3+/-0.5 h (mean +/- S.E.M.), a distribution of the central compartment Vp (3.1+/-0.3 1, mean +/- S.E.M.), and the apparent volume of distribution of the tissue compartment Vt (8.5+/-2.9 1, mean +/- S.E.M.). In the repeated exposure study, 730+/-92 mg GeO2 in 1 1 double-distilled H2O ( = 100 mg/kg/day) was given daily to rats for 4 weeks (p.o.). After sacrificing the rats, the analysis of tissue distribution showed that GeO2 was accumulated in some important organs or tissues in the body, especially the peripheral nerves and kidney. These results indicate that GeO2 could be absorbed rapidly but had a longer elimination half-life in rats. In addition, GeO2 was accumulated especially in the nerves and kidney following long-term exposure.

Animals↗

PubMed1999

No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population.

The serotonin hypothesis in schizophrenia had regained interest with the superior efficacy of clozapine in the refractory schizophrenic patients. Among the serotonin receptors, the serotonin 2A (5HT2A) receptor subtype is the most widely studied. Previous studies on the association between a silent mutation polymorphism of the 5HT2A gene (102T/C) and schizophrenia or clozapine response have yielded conflicting findings. Therefore, we investigated whether these genetic variants of the 5HT2A receptor are associated with schizophrenia or with response to clozapine treatment in a Chinese population. Ninety-seven schizophrenic patients and 101 control subjects were included in the study. The receptor variants were found at similar frequencies in schizophrenic patients and healthy control subjects. Also, we did not find the variants to influence the response to clozapine in schizophrenic patients. We suggest that the assessment method of clozapine response and the ethnicity may influence the result.

Adult↗

PubMed1999

Triflavin potentiates the antiplatelet activity of platelet activating factor receptor antagonist on activated neutrophil-induced platelet aggregation.

In this study, specific platelet activating factor (PAF) receptor antagonist ginkgolide B (BN52021) was tested for its antiplatelet activity in zymosan activated polymorphonuclear neutrophil-induced platelet aggregation. Triflavin was also tested for its antiplatelet activity compared with PAF receptor antagonist. Triflavin, an Arg-Gly-Asp-containing disintegrin purified from venom peptide inhibited platelet aggregation by interfering with the interaction of fibrinogen with the glycoprotein IIb/IIIa complex. Furthermore, we also report an efficient high resolution method for quantitative analysis of PAF using high-performance capillary electrophoresis (HPCE). The supernatant of polymorphonuclear neutrophils after their activation by opsonized zymosan induces the aggregation of washed rabbit platelets. In rabbit platelets, BN52021 (100-1000 microM) only partially inhibited activated polymorphonuclear neutrophil-induced platelet aggregation, and its maximal inhibition was estimated to be about 79%. Triflavin also partially inhibited platelet aggregation about 82% induced by activated polymorphonuclear neutrophils. Furthermore, after treatment with a combination of triflavin (0.26 microM) with various concentrations of BN52021 (4-1000 microM), the inhibitory effect of platelet aggregation was almost completely. This inhibition was greater than that produced by the individual drugs alone. These results indicate that a combination of glycoprotein IIb/IIIa complex and PAF receptor antagonist could completely inhibit activated polymorphonuclear neutrophil-induced platelet aggregation. In addition, the amount of PAF released from zymosan (6 mg/ml)-activated polymorphonuclear neutrophils was accurately calculated about 11.8+/-1.5 ng/10(6) cells, and did not further increase even at a high concentration of zymosan (10 mg/ml). These results suggest that PAF play a major role in the interaction between platelets and polymorphonuclear neutrophils. This interaction may be important in the pathogenesis of thrombosis and inflammatory diseases. Our present findings support the hypothesis that combination therapy with glycoprotein IIb/IIIa complex antagonists and PAF receptor antagonists may represent a new approach to the treatment of ischemic disorders.

Animals↗

PubMed1999

Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.

Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.

Anti-Inflammatory Agents↗

PubMed1999

Lack of significant proximal esophageal acid reflux in infants presenting with respiratory symptoms.

The effects of proximal esophageal acid reflux on upper and lower respiratory tract symptoms in infants with gastroesophageal reflux (GER) remain controversial. We studied 116 infants with either respiratory or gastrointestinal symptoms to determine whether acid reflux in the proximal esophagus plays an etiologic role in the elicitation of respiratory symptoms in comparison to causing gastrointestinal (GI) symptoms only. Sixty-two infants (age range, 1-12 months) with respiratory symptoms suggestive of GER and 54 infants with gastrointestinal symptoms only (age range, 1-10 months) were evaluated with dual level esophageal pH monitoring. Mean duration of dual-level pH monitoring in infants with respiratory symptoms was 20.4 h, and in those with GI symptoms was 20.7 h. Seventeen of 54 infants with GI symptoms only and 16 of 63 infants with respiratory symptoms had abnormal distal esophageal acid reflux indices (i.e., pH <4.0 for >5% of the duration of study). In infants with abnormal distal pH monitoring, the median proximal acid reflux index in the GI group was 4.0% in comparison to 0.95% in the respiratory group (P < 0.01 by Wilcoxon rank sum W test). Values for other reflux parameters were also higher in the GI than in the respiratory group. We conclude that reflux-associated respiratory symptoms are more likely due to mechanisms other than the mere presence of refluxed acid in the proximal esophagus.

Case-Control Studies↗

PubMed1999

Targeting of aminopeptidase N to bile canaliculi correlates with secretory activities of the developing canalicular domain.

We have used human hepatoma cell lines as an in vitro model to study the development of hepatic bile canaliculi (BC). Well-differentiated hepatoma cells cultured for 72 hours could develop characteristic spheroid structures at sites of cell-cell contact that contained tight junctions and various membrane protein markers, resembling BC found in vivo. Intact cytoskeleton was essential for this differentiation process. In the coculture experiments in which cells of different origins were populated together, BC only formed between hepatic cells and preferentially among well-differentiated cells. Poorly differentiated hepatoma cells never formed BC among themselves, but could be induced to undergo canalicular differentiation by interacting with well-differentiated cells. During BC morphogenesis, integral canalicular membrane proteins were gradually delivered and accumulated at the developing BC. Among them, targeting of aminopeptidase N (APN) seemed to correlate with activation of certain secretory functions. Specifically, only APN-positive BC supported excretion of fluorescein diacetate (FDA) and 70-kd dextran, but had no relationship with secretion of horseradish peroxidase (HRP). Targeting of another BC protein, dipeptidyl peptidase IV (DPPIV), on the other hand, bore no association with any secretory activity examined. In addition, inhibition of enzymatic activity of APN could perturb canalicular differentiation without affecting cell proliferation. Our results suggest that targeting of APN proteins may reflect or even play an important role in the development and functional maturation of the canalicular structures.

Bile Canaliculi↗

PubMed1999

Comparison of patient-controlled analgesia (PCA) with tramadol or morphine.

PURPOSE: To compared the clinical efficacy of tramadol and morphine using a patient-controlled analgesia (PCA) delivery system. METHODS: In a prospective, randomized, double blind study, we evaluated 80 adult patients scheduled for elective hip or knee arthroplasty with general inhalational anesthesia. When patients complained of pain in the recovery room, patients were randomized to receive either tramadol or morphine by titration in 30 min to achieve analgesia (VAS < or =4). Equivalent volumes containing either 30 mg x ml(-1) tramadol or 1 mg x ml(-1) morphine were used for PCA with a lockout interval of 10 min. The patients were followed six-hourly for 48 hr for VAS, satisfaction rate, analgesic dose, and side effects. RESULTS: Patients obtained adequate analgesia with either drug. More patients had very good satisfaction scores in the morphine group in the recovery room (43% vs. 23%, P<0.05) and at 24 hr (40% vs. 20%, P<0.05) than those in the tramadol group. More nausea was evident in the tramadol group (48% vs. 11% in recovery room and 28% vs. 12% in 24 hr, P<0.05) than in the morphine group. Vomiting was also more (28% vs. 5% in recovery room, 15% vs. 3% in 24 hr, P<0.05). Morphine produced more sleepiness (45% vs. 23% in recovery room, P<0.05 and 35% vs. 15% in 24 hr, P<0.05). CONCLUSION: Tramadol PCA can provide effective analgesia following major orthopedic surgery provided sufficiently high doses are given for loading and by patient demand. However, the incidence of nausea/vomiting is also higher causing decreased satisfaction.

Adult↗

PubMed1999

Spontaneous resolution of internal jugular vein thrombosis in a Salmonella neck abscess patient.

This article describes a rare case of Salmonella neck abscess complicated by internal jugular vein thrombosis in a 51-year-old patient with previously undiagnosed diabetes. The patient was discharged without any complications after a combination of medical and surgical treatment. Also discussed here are the clinical manifestations, imaging findings, and spontaneous resolution of the internal jugular vein thrombosis. Being immunocompromised is a critical predisposing factor for Salmonella neck abscess. Patient recovery is largely determined by proper incision, drainage of pus and adequate intravenous antibiotics according to bacterial sensitivity tests. Detection of an internal jugular vein thrombosis does not signify a poor prognosis. Spontaneous resolution of thrombosis is encountered after treating the infection.

Abscess↗

PubMed1999

Spectral and conformational analysis of deoxyadenosine adducts derived from syn- and anti-Dibenzo[a,l]pyrene diol epoxides: fluorescence studies.

Low-temperature fluorescence spectra and results of conformational studies with trans-syn-, cis-syn-, trans-anti-, and cis-anti-dibenzo[a,l]pyrene diol epoxide (DB[a,l]PDE)-derived deoxyadenosine (dA) adducts are presented and compared with those previously obtained for the stereoisomeric DB[a,l]P tetrols [Jankowiak, R., et al. (1997) Chem. Res. Toxicol. 10, 677-686]. In contrast to DB[a,l]P tetrols, for which only trans isomers exhibited two conformers, all stereoisomeric dA adducts adopt two different conformations with either half-chair or half-boat structures for the cyclohexenyl ring, and an "open"- or "folded"-type configuration between dA and the DB[a,l]P moiety. The major conformations observed for trans-syn-, cis-syn-, and cis-anti-DB[a,l]PDE-14-N(6)dA could be assigned on the basis of the previous calculations for the DB[a,l]P tetrols. The major conformers of the trans-syn- and cis-syn-DB[a, l]PDE-14-N(6)dA adducts exist in conformations I and II, with their fluorescence origin bands at approximately 382 and approximately 389 nm, respectively. In conformation I, the cyclohexenyl ring adopts a half-boat structure with dA in a pseudoaxial position (an open configuration), whereas the cyclohexenyl ring in conformation II adopts a half-chair structure with dA in pseudoequatorial position (a folded configuration). The major conformation of cis-anti-DB[a, l]PDE-14-N(6)dA, with its origin band at approximately 389 nm, was also assigned as a folded-type configuration with a half-chair structure in the cyclohexenyl ring. Molecular mechanics and dynamical simulations were performed for interpretation of the low-temperature fluorescence spectra and (1)H NMR coupling constants observed for the trans-anti-DB[a,l]PDE-14-N(6)dA adduct. The major conformer of this adduct has a half-chair structure in the cyclohexenyl ring, but a deviation from planarity in the fjord region different from that of conformer II of cis-anti-DB[a, l]PDE-N(6)dA. This new structure is labeled as conformer II'. Its (0, 0) fluorescence band is at 388.1 and 388.3 nm in ethanol and glycerol/water glasses, respectively, consistent with the folded-type configuration revealed by the calculations. The fluorescence line-narrowed spectra reveal that the trans-syn-, cis-syn-, trans-anti-, and cis-anti-DB[a,l]PDE-14-N(6)dA adducts can be distinguished. Thus, their spectra should prove useful for identification of DB[a,l]P-DNA adducts formed at low levels in biological samples.

Benzopyrenes↗

PubMed1999

Structure elucidation of the adducts formed by fjord region Dibenzo[a,l]pyrene-11,12-dihydrodiol 13,14-epoxides with deoxyguanosine.

(+/-)-anti-Dibenzo[a,l]pyrene-11,12-dihydrodiol 13,14-epoxide {(+/-)-anti-DB[a,l]PDE} was reacted with deoxyguanosine (dG) in dimethylformamide at 100 degrees C for 30 min, and two sets of adducts were isolated: a mixture of (+/-)-anti-cis- & -trans-N(2)dG (43%) and a mixture of (+/-)-anti-cis- & -trans-N7Gua (45%). Both are mixtures of four stereoisomers that cannot be separated by HPLC. Similarly, (+/-)-syn-DB[a,l]PDE was reacted with dG under the same conditions, and (+/-)-syn-cis- & -trans-N(2)dG (38%) and (+/-)-syn-cis- & -trans-N7Gua (59%) were obtained. The structures of the adducts were determined by a combination of NMR and fast atom bombardment mass spectrometry. By reacting (-)-anti-DB[a,l]PDE or (+)-syn-DB[a,l]PDE with dG under the same conditions, however, optically pure N(2)dG and N7Gua isomers were obtained: (-)-anti-cis-N(2)dG (12%), (-)-anti-trans-N(2)dG (17%), (-)-anti-trans-N7Gua (43%), (+)-syn-cis-N(2)dG (7%), (+)-syn-trans-N(2)dG (3%), (+)-syn-cis-N7Gua (36%), and (+)-syn-trans-N7Gua (22%). The structures of the optically pure adducts were assigned by NMR. syn- and anti-DB[a,l]PDE-N(2)dG adducts can be distinguished by fluorescence line-narrowing spectroscopy (FLNS). Moreover, distinction between cis- and trans-stereochemistry of the adducts is also straightforward by FLNS, because the FLN spectra for the four DB[a,l]PDE-N(2)dG adducts, anti-cis, anti-trans, syn-cis, and syn-trans, are spectroscopically unique.

Chromatography, High Pressure Liquid↗

PubMed1999

Hepatitis C virus infection among short-term intravenous drug users in southern Taiwan.

The purpose of this study was to determine the correlation between the prevalence of hepatitis C virus (HCV) infection with duration of drug use and other risk factors among drug users. This survey covered 899 male drug users from Kaohsiung Narcotic Abstention Institute and Kaohsiung prison. The prevalence of positive anti-HCV was 67.2% among intravenous drug users (IVDU) and 14.7% among non-intravenous drug users (non-IVDU). Among intravenous (IV) drug users, age and duration of drug use were independently related to HCV seropositivity. Seroprevalence rate for HCV in the IVDU group increased with increasing duration of injection use within the first seven years of drug use. However, the steepest trajectory in seroprevalence of HCV infection occurred within the first four months. Due to the high rate of HCV infection among drug users, investigation of risk behaviors should be routine in such a group. A high frequency of HCV infection was also found among short-term injectors, which indicated that early risk reduction intervention was an important measure in moderating HCV infection.

Adolescent↗

PubMed1999

Increased colonic ornithine decarboxylase activity in inflammatory bowel disease in children.

The risk of colorectal carcinoma is increased in pediatric-onset inflammatory bowel disease (IBD). There is little information available regarding the colonic mucosal proliferative state in children with IBD. The aim of this study was to assess colonic ornithine decarboxylase (ODC) activity, a marker of cell proliferation, in pediatric IBD patients. ODC activity was assessed in colonic mucosa from 23 children (7 with ulcerative colitis, 9 with Crohn's disease, and 7 controls) undergoing colonoscopic examination. ODC activities were then compared with degree of inflammation of biopsied samples. ODC activities in patients with and without corticosteroid treatment were also analyzed. The mucosal ODC activities of sigmoid colon and rectum were significantly higher (2.5- to 4-fold) in both ulcerative colitis and Crohn's disease. The higher ODC activity was associated with increased mucosal inflammation. Moreover, treatment with corticosteroids decreased the ODC activity. In conclusion, using ODC activities as a marker of cell proliferation, our results suggest that there is a higher colonic mucosal proliferative state in children with IBD. The increased ODC activities were associated with increased colonic mucosal inflammation. Colonic mucosal ODC activity may provide an additional parameter to access the therapeutic efficacy of corticosteroid treatment in pediatric IBD patients.

Adolescent↗

PubMed1999

The antiplatelet activity of PMC, a potent alpha-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase.

PMC, a potent alpha-tocopherol derivative, dose-dependently (5-25 microM) inhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets stimulated by collagen. PMC (10 and 25 microM) significantly inhibited collagen-stimulated thromboxane A2 (TxA2) formation in human platelets. On the other hand, PMC (25 and 100 microM) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 microM) did not affect the thromboxane synthetase activity of aspirin-treated platelet microsomes. PMC (10 and 25 microM) markedly inhibited the exogenous arachidonic acid (100 microM)-induced prostaglandin E2 (PGE2) formation in the presence of imidazole (600 microM) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclooxygenase activity, which leads to reduced prostaglandin formation; this, in turn, is followed by a reduction of TxA2 formation, and finally inhibition of [Ca2+]i mobilization and ATP-release.

Antioxidants↗

PubMed1999

Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.

Animals↗

PubMed1999

Calcium binding mode of gamma-carboxyglutamic acids in conantokins.

Conantokin-T (con-T) and conantokin-G (con-G) are two highly homologous peptide toxins found in Conus venom. The former is a 21-residue peptide with four gamma-carboxyglutamic acid (Gla) residues (at positions 3, 4, 10 and 14), while the latter is a 17-residue peptide with five gamma-carboxyglutamic acid residues (at positions 3, 4, 7, 10 and 14). Despite the apparent similarity in number and relative positions of the gamma-carboxyglutamic acid residues, (113)Cd-NMR studies indicated a distinct metal binding behavior for con-G and con-T. There appears to be four binding sites in con-G in contrast to one metal binding site in con-T. To elucidate the mode of calcium binding by the gamma-carboxyglutamic acid residues in these conantokins, we designed various analogous peptides with their gamma-carboxyglutamic acid replaced by other amino acid residues. (113)Cd-NMR experiments on conantokin analogues reveal that the major difference in the number of metal binding sites between con-G and con-T is due to the residue at position 7. We also performed molecular simulations to calculate the relative binding free energies of several potential binding sites. Based on our theoretical and experimental results, we propose a 'four-site' binding model for conantokin-G and a 'single-site' binding model for conantokin-T.

1-Carboxyglutamic Acid↗