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John C. Burnett - One of the best experts on this subject based on the ideXlab platform.
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Natriuretic Peptide Structures.
2013Co-Authors: Fernando L. Martin, Jeson S. Sangaralingham, Brenda K. Huntley, Paul M. Mckie, Tomoko Ichiki, Horng H. Chen, Josef Korinek, Gerald E. Harders, John C. BurnettAbstract:Amino acid sequence of mature C-type natriuretic peptide (CNP), Dendroaspis natriuretic peptide (DNP) and the designer natriuretic peptide, CD-NP.
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CD-NP: An Innovative Designer Natriuretic Peptide Activator of Particulate Guanylyl Cyclase Receptors for Cardiorenal Disease
Current Heart Failure Reports, 2010Co-Authors: Paul M. Mckie, S. Jeson Sangaralingham, John C. BurnettAbstract:The natriuretic peptide (NP) family consists of structurally similar, although physiologically distinct, peptides that play an important role in cardiorenal homeostasis. CD-NP is a novel chimeric natriuretic peptide developed by the Mayo Clinic, in which the 15-amino acid COOH-terminus of Dendroaspis NP is fused to C-type NP. CD-NP is a dual activator of NP receptors A and B, and therefore, possesses the strong antiproliferative and antifibrotic properties of C-type NP with the potent natriuretic, diuretic, and aldosterone-inhibiting properties of Dendroaspis NP. CD-NP has favorable cardiorenal properties when compared to recombinant B-type NP (nesiritide), including preservation of glomerular filtration rate with minimal blood pressure-lowering effects. Thus, CD-NP has emerged as an appealing novel therapeutic strategy for heart failure. The endogenous NP system, the development rationale for CD-NP, as well as in vitro, animal, and human studies and future directions will be reviewed.
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Natriuretic peptides and therapeutic applications
Heart Failure Reviews, 2007Co-Authors: John C. BurnettAbstract:Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.
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A pilot study of Dendroaspis natriuretic peptide in aneurysmal subarachnoid hemorrhage.
Neurosurgery, 2004Co-Authors: Vini G. Khurana, Denise M. Heublein, Eelco F. M. Wijdicks, Robyn L. Mcclelland, Fredric B. Meyer, David G. Piepgras, John C. BurnettAbstract:OBJECTIVE: Hypovolemia after aneurysmal subarachnoid hemorrhage (SAH) may be mediated by natriuretic peptides and can further impair cerebral perfusion in dysautoregulated and vasospastic arterial territories. Dendroaspis natriuretic peptide (DNP), derived from the venom of Dendroaspis augusticeps, the Green Mamba snake, has recently been discovered in human plasma and atrial myocardium. There is no information regarding the presence or putative role of this peptide in patients with aneurysmal SAH. METHODS: A sensitive and specific DNP radioimmunoassay was performed on venous blood samples obtained on post-SAH Days 1, 3, and 7 from 10 consecutive SAH patients (cases) and randomly from 9 healthy volunteers (controls). Clinical and laboratory data, including daily serum sodium concentration and fluid balance, were collected prospectively up to 7 days after the ictus. RESULTS: Increase in plasma DNP levels occurred in five (63%) of eight patients who had DNP levels measured on Days 1 and 3 (mean increase, 29%). An increase in DNP level was significantly associated with development of a negative fluid balance (P = 0.003) and hyponatremia (P = 0.008). Three (75%) of the four patients who developed cerebral vasospasm during this study experienced an increase in DNP levels from Days 1 to 3. CONCLUSION: The present study is the first to find a significant association between elevated levels of DNP, a new member of the natriuretic peptide family, and the development of diuresis and natriuresis in patients with aneurysmal SAH. Our findings warrant further investigation by means of a large-scale, prospective, case-control study.
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Natriuretic peptide receptors and neutral endopeptidase in mediating the renal actions of a new therapeutic synthetic natriuretic peptide Dendroaspis natriuretic peptide.
Journal of the American College of Cardiology, 2002Co-Authors: Horng H. Chen, John G. Lainchbury, John C. BurnettAbstract:Abstract Objectives The objectives of the current study were to define for the first time the roles of the natriuretic peptide (NP) receptors and neutral endopeptidase (NEP) in mediating and modulating the renal actions of Dendroaspis natriuretic peptide (DNP), a new therapeutic synthetic NP. Background Recent reports have advanced the therapeutic potential of a newly described synthetic NP called DNP. Dendroaspis natriuretic peptide is a 38-amino acid peptide recently isolated from the venom of Dendroaspis augusticeps (the green mamba snake). Methods Synthetic DNP was administered intra-renally at 5 ng/kg/min to 11 normal anesthetized dogs, 5 of which received the NP receptor antagonist HS-142-1 (3 mg/kg intravenous bolus) while the remaining 6 dogs received an infusion of the NEP inhibitor, candoxatrilat (8 and 80 μg/kg/min) (Pfizer, Sandwich United Kingdom). Results Intra-renal DNP resulted in marked natriuresis associated with increased urinary cyclic guanosine monophosphate excretion (UcGMPV), glomerular filtration rate (GFR), and renal blood flow (RBF) and decreased distal fractional sodium reabsorption (FNaR) compared with baseline. HS-142-1 attenuated the natriuretic response to DNP, resulting in decreased UcGMPV, GFR, and RBF and increased distal FNaR. In contrast, low and high doses of NEP inhibitor did not potentiate the renal actions of DNP. Conclusions We report that the NP receptor blockade attenuated the renal actions of synthetic DNP and that the NEP inhibitor did not alter the renal response to DNP. This latter finding is a unique property of synthetic DNP, as distinguished from other known NPs, supporting its potential as a therapeutic agent.
Vijay V Kakkar - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the role of proline residues flanking the RGD motif of dendroaspin, an inhibitior of platelet aggregation and cell adhesion
Biochemical Journal, 2001Co-Authors: Yingqing Sun, Eva I. Hyde, Dazhuang Shang, Beth Wattam, Sofia Egglezou, Tracy Hughes, Mike Scully, Vijay V KakkarAbstract:The effect of a panel of proline mutants of dendroaspin, an inhibitor of platelet aggregation and cell adhesion, including A(42)-dendroaspin, A(47)-dendroaspin, A(49)-dendroaspin, A(42,47)-dendroaspin and A(47,49)-dendroaspin, was investigated using platelet-aggregation and cell-adhesion assays. Here we show that a single alanine-for-proline substitution did not affect potency when measured as the ability either to inhibit platelet aggregation induced by ADP (IC(50) approximately 170 nM) or to block transfected A375-SM cell adhesion to fibrinogen in the presence of Mn(2+) as compared with wild-type dendroaspin. By comparison, double proline substitution with alanines significantly reduced the potency in both assays by approx. 5-8-fold. These observations, therefore, suggest that proline residues flanking the RGD motif in dendroaspin and other RGD-containing venom proteins, e.g. disintegrins, may contribute to maintaining a favourable conformation for the solvent-exposed RGD site for its recognition by integrin receptors.
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dendroaspin a potent integrin receptor inhibitor from the venoms of Dendroaspis viridis and d jamesonii
Biochemical Society Transactions, 1993Co-Authors: Janice A Williams, Salman Rahman, Christopher Keating, Vijay V KakkarAbstract:In the last five years the identification of numerous adhesion receptors, and the recognition motifs within their physiological glycoprotein ligands, have elucidated some of the basic principles underlying cell-cell and cell-matrix interactions (1). Most adhesion receptors belong to the integrin supergene family, eg. a11bP3, avP3 (2). A key mechanism common to a number of integrin-ligand interactions involves the recognition of short aspartate-containing sequences or motifs (3), which include the ubiquitous sequence Arg-Gly-Asp (RGD). In this regard, a major breakthrough has been the discovery of a family of small (6-9kDa). RGD-containing polypeptides derived from the venoms of pit vipers, potent inhibitors of integrin-ligand interactions and thus termed disintegrins (4,5,6,7). In the present study we have identified, purified and sequenced a potent, novel disintegrin-like polypeptide from the venom of D.viridis, and an identical polypeptide from D.jamesonii. This polypeptide was originally described as a nontoxic neurotoxin (8) and was identified by us as containing an RGD motif during a search of the Protein Identification Resource (PIR), NBRF, Washington. The RGD motif was found to be held within the 13 amino acid-loop CFTPRCDMPGPYC, which is highly similar to that from the disintegrin, kismn CRIPRGDMPDDRC (9). whereas the remainder of the molecule showed high sequence identiry with the short-chain neurotoxins pable 1.). We have developed a single step reverse phase HPLC purification of dendroaspin (Fig.1). from the whole venoms of Dendroaspis viridis and D. jamesonii kaimosae (Latoxan, France), by chromatography on a Vydac C-18 reverse phase column (6). A single active fraction was identified for each venom (Figl.). Active fractions were identified by testing for the inhibition of ADPinduced fibrinogen-mediated platelet aggregation in platelet rich plasma (PRP) as previously described (6). The amino acid sequence, as published by Joubert et a1 (8), was confirmed using established techniques (10). Table 1. illustrates the degree of homology with the neurotoxin erabutoxin b and the disintegrins, albolabrin and elegantin (6). There is minimal homology with the disintegrins outside the RGD-loop and minimal homology with the neurotoxins within the loop. Isoelectric focusing experiments were performed using PAG (Phmacia) over the ranges pH 5.5-8.5 and pH 3.5-9.5. Running
Kurt Wüthrich - One of the best experts on this subject based on the ideXlab platform.
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Nuclear Magnetic Resonance Solution Structure of Dendrotoxin K from the Venom of Dendroaspis polylepis polylepis
Journal of molecular biology, 1993Co-Authors: Kurt D. Berndt, Peter Güntert, Kurt WüthrichAbstract:Nuclear-Magnetic-Resonance Solution Structure of Dendrotoxin-K from the Venom of Dendroaspis-Polylepis-Polylepis
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The program ASNO for computer-supported collection of NOE upper distance constraints as input for protein structure determination
Journal of Biomolecular NMR, 1993Co-Authors: Peter Güntert, Kurt D. Berndt, Kurt WüthrichAbstract:A new program, ASNO (‘ AS sign NO es’), for computer-supported NOE cross-peak assignments is described. ASNO is used for structure refinement in several rounds of NOESY cross-peak assignments and 3D structure calculations, where the preliminary structures are used as a reference to resolve ambiguities in NOE assignments which are otherwise based on the chemical shifts available from the sequence-specific resonance assignments. The practical use of ASNO for proteins is illustrated with the structure determination of Dendrotoxin K from Dendroaspis polylepis polylepis .
Horng H. Chen - One of the best experts on this subject based on the ideXlab platform.
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Natriuretic Peptide Structures.
2013Co-Authors: Fernando L. Martin, Jeson S. Sangaralingham, Brenda K. Huntley, Paul M. Mckie, Tomoko Ichiki, Horng H. Chen, Josef Korinek, Gerald E. Harders, John C. BurnettAbstract:Amino acid sequence of mature C-type natriuretic peptide (CNP), Dendroaspis natriuretic peptide (DNP) and the designer natriuretic peptide, CD-NP.
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Natriuretic peptide receptors and neutral endopeptidase in mediating the renal actions of a new therapeutic synthetic natriuretic peptide Dendroaspis natriuretic peptide.
Journal of the American College of Cardiology, 2002Co-Authors: Horng H. Chen, John G. Lainchbury, John C. BurnettAbstract:Abstract Objectives The objectives of the current study were to define for the first time the roles of the natriuretic peptide (NP) receptors and neutral endopeptidase (NEP) in mediating and modulating the renal actions of Dendroaspis natriuretic peptide (DNP), a new therapeutic synthetic NP. Background Recent reports have advanced the therapeutic potential of a newly described synthetic NP called DNP. Dendroaspis natriuretic peptide is a 38-amino acid peptide recently isolated from the venom of Dendroaspis augusticeps (the green mamba snake). Methods Synthetic DNP was administered intra-renally at 5 ng/kg/min to 11 normal anesthetized dogs, 5 of which received the NP receptor antagonist HS-142-1 (3 mg/kg intravenous bolus) while the remaining 6 dogs received an infusion of the NEP inhibitor, candoxatrilat (8 and 80 μg/kg/min) (Pfizer, Sandwich United Kingdom). Results Intra-renal DNP resulted in marked natriuresis associated with increased urinary cyclic guanosine monophosphate excretion (UcGMPV), glomerular filtration rate (GFR), and renal blood flow (RBF) and decreased distal fractional sodium reabsorption (FNaR) compared with baseline. HS-142-1 attenuated the natriuretic response to DNP, resulting in decreased UcGMPV, GFR, and RBF and increased distal FNaR. In contrast, low and high doses of NEP inhibitor did not potentiate the renal actions of DNP. Conclusions We report that the NP receptor blockade attenuated the renal actions of synthetic DNP and that the NEP inhibitor did not alter the renal response to DNP. This latter finding is a unique property of synthetic DNP, as distinguished from other known NPs, supporting its potential as a therapeutic agent.
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Renal actions of synthetic Dendroaspis natriuretic peptide.
Kidney international, 1999Co-Authors: Ondrej Lisy, Horng H. Chen, Michihisa Jougasaki, Denise M. Heublein, John A. Schirger, Paul W. Wennberg, John C. BurnettAbstract:Renal actions of synthetic Dendroaspis natriuretic peptide. Background Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps , is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). DNP-like immunoreactivity (DNP-LI) was reported to be present in human plasma and atrial myocardium and to be elevated in human congestive heart failure. Although previously named DNP, it remains unknown if DNP is natriuretic or if is it present in canine plasma, urine, and atrial myocardium. Method Studies were performed in vivo in anesthetized dogs ( N = 6) using intravenous infusion of synthetic DNP at 10 and 50 ng/kg/min. Employing a sensitive and specific radioimmunoassay for DNP, the presence of DNP-like peptide was assessed in the canine plasma and urine before, during, and following the administration of exogenous synthetic DNP. Additionally, we performed immunohistochemical studies using the indirect immunoperoxidase method with polyclonal DNP antiserum in normal atrial myocardium ( N = 10). Atrial concentrations of DNP-LI were also assessed. Results We report that DNP is markedly natriuretic and diuretic, which, like ANP and BNP, is associated with the increase in urinary and plasma cGMP. DNP-like peptide is also detected in canine plasma, urine, and atrial myocardium. Conclusion These studies establish that DNP is a potent natriuretic and diuretic peptide with tubular actions linked to cGMP and that DNP may play a physiological role in the regulation of sodium excretion.
Janice A Williams - One of the best experts on this subject based on the ideXlab platform.
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Three-dimensional structure of the RGD-containing neurotoxin homologue dendroaspin
Nature Structural Biology, 1994Co-Authors: Michael J Sutcliffe, Mahesh Jaseja, Eva I. Hyde, Xinjie Lu, Janice A WilliamsAbstract:Dendroaspin is a short chain neurotoxin homologue from the venom of Elapidae snakes, which lacks neurotoxicity. Unlike neurotoxins, it contains an Arg-Gly-Asp-(RGD)-motif and functions as an inhibitor of platelet aggregation and platelet adhesion with comparable potency to the disintegrins from the venoms of Viperidae . We have determined the structure of dendroaspin in solution using NMR spectroscopy. The structure contains a core similar to that of short chain neurotoxins, but with a novel arrangement of loops and a solvent-exposed RGD-motif. Dendroaspin is thus an integrin antagonist with a well defined fold different from that of the disintegrins, based on the neurotoxin scaffold.
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dendroaspin a potent integrin receptor inhibitor from the venoms of Dendroaspis viridis and d jamesonii
Biochemical Society Transactions, 1993Co-Authors: Janice A Williams, Salman Rahman, Christopher Keating, Vijay V KakkarAbstract:In the last five years the identification of numerous adhesion receptors, and the recognition motifs within their physiological glycoprotein ligands, have elucidated some of the basic principles underlying cell-cell and cell-matrix interactions (1). Most adhesion receptors belong to the integrin supergene family, eg. a11bP3, avP3 (2). A key mechanism common to a number of integrin-ligand interactions involves the recognition of short aspartate-containing sequences or motifs (3), which include the ubiquitous sequence Arg-Gly-Asp (RGD). In this regard, a major breakthrough has been the discovery of a family of small (6-9kDa). RGD-containing polypeptides derived from the venoms of pit vipers, potent inhibitors of integrin-ligand interactions and thus termed disintegrins (4,5,6,7). In the present study we have identified, purified and sequenced a potent, novel disintegrin-like polypeptide from the venom of D.viridis, and an identical polypeptide from D.jamesonii. This polypeptide was originally described as a nontoxic neurotoxin (8) and was identified by us as containing an RGD motif during a search of the Protein Identification Resource (PIR), NBRF, Washington. The RGD motif was found to be held within the 13 amino acid-loop CFTPRCDMPGPYC, which is highly similar to that from the disintegrin, kismn CRIPRGDMPDDRC (9). whereas the remainder of the molecule showed high sequence identiry with the short-chain neurotoxins pable 1.). We have developed a single step reverse phase HPLC purification of dendroaspin (Fig.1). from the whole venoms of Dendroaspis viridis and D. jamesonii kaimosae (Latoxan, France), by chromatography on a Vydac C-18 reverse phase column (6). A single active fraction was identified for each venom (Figl.). Active fractions were identified by testing for the inhibition of ADPinduced fibrinogen-mediated platelet aggregation in platelet rich plasma (PRP) as previously described (6). The amino acid sequence, as published by Joubert et a1 (8), was confirmed using established techniques (10). Table 1. illustrates the degree of homology with the neurotoxin erabutoxin b and the disintegrins, albolabrin and elegantin (6). There is minimal homology with the disintegrins outside the RGD-loop and minimal homology with the neurotoxins within the loop. Isoelectric focusing experiments were performed using PAG (Phmacia) over the ranges pH 5.5-8.5 and pH 3.5-9.5. Running