Surface characterization and evaluation of biofilm growth on reverse osmosis membranes functional... more Surface characterization and evaluation of biofilm growth on reverse osmosis membranes functionalized with bio-active peptides Marina-Yamit Lutskiy1, Shani Avneri1, Roza Fainshtein1, Sophia Belfer1, Zeev Ronen2, Roni Kasher1 1Department of Desalination & Water Treatment and 2Department of Hydrology & Environmental Microbiology, Zuckerberg Institute for Water Research, The Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sde Boker 84990, Israel A major problem in reverse osmosis (RO) and nanofiltration (NF) technologies is fouling, and the most rigorous type of fouling is biofouling. In our recent study we have developed a novel approach to control biofouling of RO membranes which is based on multivalent linking of antimicrobial peptides (AMPs) to the membrane surface and inhibition of biofilm formation (Fig 1). Figure 1: Schematic illustration of bio-active peptides immobilized onto RO membranes through maleimide-thiol chemistry. Here we present a thorou...
Swelling of the active layer of reverse osmosis (RO) membranes has an important effect on permeat... more Swelling of the active layer of reverse osmosis (RO) membranes has an important effect on permeate water flux. The effects of organic- and biofouling on the swelling of the RO membrane active layer and the consequent changes of permeate flux are examined here. A cross-linked aromatic oligoamide film that mimics the surface chemistry of an RO polyamide membrane was synthesized stepwise on gold-coated surfaces. Foulant adsorption to the oligoamide film and its swelling were measured with a quartz crystal microbalance, and the effects of fouling on the membrane's performance were evaluated. The foulants were extracellular polymeric substances (EPS) extracted from fouled RO membranes and organic compounds of ultrafiltration permeate (UFP) from a membrane bioreactor used to treat municipal wastewater. The adsorbed foulants affected the swelling of the cross-linked oligoamide film differently. EPS had little effect on the swelling of the oligoamide film, whereas UFP significantly impaired swelling. Permeate flux declined more rapidly under UFP fouling than it did under EPS. Foulant adsorption was shown to diminish swelling of the aromatic oligoamide surfaces. Among the already known RO membrane fouling mechanisms, a novel RO fouling mechanism is proposed, in which foulant-membrane interactions hinder membrane swelling and thus increase hydraulic resistance.
Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine rec... more Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. In the following we review multi-phase research of the design, synthesis and structure analysis of peptides that bind alpha-BTX and inhibit its binding to AChR. Structure-based design concomitant with biological information of the alpha-BTX/AChR system yielded 13-mer peptides that bind to alpha-BTX with high affinity and are potent inhibitors of alpha-BTX binding to AChR (IC(50) of 2 nM). X-Ray and NMR spectroscopy reveal that the high-affinity peptides fold into an anti-parallel beta-hairpin structure when bound to alpha-BTX. The structures of the bound peptides and the homologous loop of acetylcholine binding protein, a soluble analog of AChR, are remarkably similar. Their superposition indicates that the toxin wraps around the binding-site loop, and in addition, binds tightly at the interface of tw...
Proceedings of the National Academy of Sciences, 2001
Snake-venom ␣-bungarotoxin is a member of the ␣-neurotoxin family that binds with very high affin... more Snake-venom ␣-bungarotoxin is a member of the ␣-neurotoxin family that binds with very high affinity to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. The structure of the complex between ␣-bungarotoxin and a 13-mer peptide (WRYYES-SLEPYPD) that binds the toxin with high affinity, thus inhibiting its interactions with AChR with an IC 50 of 2 nM, has been solved by 1 H-NMR spectroscopy. The bound peptide folds into a -hairpin structure created by two antiparallel -strands, which combine with the already existing triple-stranded -sheet of the toxin to form a five-stranded intermolecular, antiparallel -sheet. Peptide residues Y3 P , E5 P , and L8 P have the highest intermolecular contact area, indicating their importance in the binding of ␣-bungarotoxin; W1 P , R2 P , and Y4 P also contribute significantly to the binding. A large number of characteristic hydrogen bonds and electrostatic and hydrophobic interactions are observed in the complex. The high-affinity peptide exhibits inhibitory potency that is better than any known peptide derived from AChR, and is equal to that of the whole ␣-subunit of AChR. The high degree of sequence similarity between the peptide and various types of AChRs implies that the binding mode found within the complex might possibly mimic the receptor binding to the toxin. The design of the high-affinity peptide was based on our previous findings: (i) the detection of a lead peptide (MRYYES-SLKSYPD) that binds ␣-bungarotoxin, using a phage-display peptide library, (ii) the information about the three-dimensional structure of ␣-bungarotoxin͞lead-peptide complex, and (iii) the amino acid sequence analysis of different AChRs.
The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since it... more The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since its hydrophobic character hampers its successful 3 Department of Organic Chemistry crystallization. There have been several attempts to 4 Department of Immunology crystallize the extracellular domain of AChR ␣ subunit Weizmann Institute of Science and most recently, the X-ray structure of an acetylcho-Rehovot 76100 line binding protein (AChBP), a water-soluble homolog Israel of the nicotinic AChR ligand binding domain isolated 5 Department of Molecular and Cellular from snail, has been solved (Brejc et al., 2001). The high Neurobiology affinity and specific interaction of ␣-BTX with AChR has Vrije Universiteit been of considerable importance in the study of the De Boelelaan 1087 ligand binding site of AChR. The ligand binding site of 1081 HV Amsterdam AChR is located mainly at the ␣ subunit, in the vicinity The Netherlands of Cys192 and Cys193 (Kao et al., 1984; Neumann et 6 Division of Molecular Carcinogenesis al., 1985), though residues in the interface of neighboring Netherlands Cancer Institute subunits contribute also to the binding site (Changeux Plesmanlaan 121 and Edelstein, 1998; Karlin and Akabas, 1995 and refer-1066 CX Amsterdam ences cited therein). Short synthetic peptides derived The Netherlands from this region of the AChR ␣ subunit were shown to bind ␣-BTX (Lentz, 1995; Neumann et al., 1986a). A 12mer synthetic peptide corresponding to residues 185-196 of the AChR, and encompassing the two tandem Summary cysteines, was found to bind agonists specifically and to inhibit the binding of ␣-BTX to AChR with an IC 50 of We have determined the crystal structure at 1.8 Å reso-10 Ϫ4 M (Neumann et al., 1986a, 1986b).
We describe a novel approach to develop peptides with estrogen like activity using a monoclonal a... more We describe a novel approach to develop peptides with estrogen like activity using a monoclonal antibody specific to estradiol (mAb E2-15) for the affinity selection of phage displayed peptides from a combinatorial peptide library. Based on the sequences of the selected phage, we synthesized a 15-mer linear peptide LPALDPTKRWFFETK which was derivatized to a 23 mer cyclic peptide CAELPALDPT-KRWFFETKPPPPC. Both peptides displayed estrogen-like activity according to the following criteria:(i) in inhibiting the binding of [ 3 H]estradiol to mAb E2-15 and to estrogen receptor (ER)␣; (ii) in inducing transcriptional activity in MCF7 human breast cancer cells transfected with an estrogen receptor element luciferase construct and (iii) in causing an increase in creatine kinase specific activity in rat tissues in vivo. This approach can be employed to design peptide mimetic for other hormones as well.
Currently used antiestrogenic drugs against hormone-dependent breast cancer, and estrogenic drugs... more Currently used antiestrogenic drugs against hormone-dependent breast cancer, and estrogenic drugs used in treatment of osteoporosis, are associated with risk factors. Therefore, there is a strong need to develop selective estrogen receptor modulators with better tissue selectivity. In a recent study (Peptides, 2002, Vol. 3, 573-580), we used a monoclonal antibody to estradiol (mAb-E2) to screen a phage-display peptide library. We identified a 15-mer peptide (peptide H5) that recognizes mAb-E2 (IC 50 1 M) and estrogen receptor (ER)␣ (IC 50 500 M) but not ER, and displays estrogen-like activity in vitro and in vivo. In this study, we designed and prepared peptides based on peptide H5, which possess improved estrogenic activity, by evaluating their binding to mAb-E2 and to ERs. Initially, we determined the minimal binding sequence of peptide H5 capable of binding mAb-E2 and ER. Subsequently, systematic single-residue replacements of the minimal sequence, followed by multiple-residue replacements, yielded hexa-and heptapeptides with increased affinities to mAb-E2 and to ER. The most promising peptides, VSWFFE (EMP-1) and VSWFFED (EMP-2) (EMP: estrogen-mimetic peptide), bind mAb-E2 with high affinity (IC 50 of 6 and 30 nM, respectively), recognize ERs with increased affinity (IC 50 of 100 M for ER␣, and 100 -250 M for ER), and possess estrogenic activity in vivo. The short peptides described in this study may be used as potential lead compounds for developing new ER ligands.
Design and synthesis of peptides that bind α-bungarotoxin with high affinity and mimic the three-... more Design and synthesis of peptides that bind α-bungarotoxin with high affinity and mimic the three-dimensional structure of the binding-site of acetylcholine receptor ARTICLE in BIOPHYSICAL CHEMISTRY · FEBRUARY 2003 Impact Factor: 1.99 · Abstract a-Bungarotoxin (a-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. In the following we review multi-phase research of the design, synthesis and structure analysis of peptides that bind a-BTX and inhibit its binding to AChR. Structurebased design concomitant with biological information of the a-BTXyAChR system yielded 13-mer peptides that bind to a-BTX with high affinity and are potent inhibitors of a-BTX binding to AChR (IC of 2 nM). X-Ray and NMR 50 spectroscopy reveal that the high-affinity peptides fold into an anti-parallel b-hairpin structure when bound to a-BTX. The structures of the bound peptides and the homologous loop of acetylcholine binding protein, a soluble analog of AChR, are remarkably similar. Their superposition indicates that the toxin wraps around the binding-site loop, and in addition, binds tightly at the interface of two of the receptor subunits and blocks access of acetylcholine to its binding site. The procedure described in this article may serve as a paradigm for obtaining high-affinity peptides in biochemical systems that contain a ligand and a receptor molecule. ᮊ -binding protein ૾ The sad news about John Edsall's passing reached us soon after his death. We are sorry that he was not able to celebrate his 100th birthday with us, but hope that he was able to enjoy the manuscripts that were sent to him directly, and that this dedicatory volume will be a fitting tribute.
... We have therefore turned to ran-dom combinatorial libraries and employed phage-display peptid... more ... We have therefore turned to ran-dom combinatorial libraries and employed phage-display peptide libraries to select peptides that interact specifically with a ... 5. Neumann D, Gershoni GM, Fridkin M, Fuchs S. Antibodies to syn-thetic peptides as probes for the binding site on the a ...
Acta Crystallographica Section A Foundations of Crystallography, 2002
The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since it... more The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since its hydrophobic character hampers its successful 3 Department of Organic Chemistry crystallization. There have been several attempts to 4 Department of Immunology crystallize the extracellular domain of AChR ␣ subunit Weizmann Institute of Science and most recently, the X-ray structure of an acetylcho-Rehovot 76100 line binding protein (AChBP), a water-soluble homolog Israel of the nicotinic AChR ligand binding domain isolated 5 Department of Molecular and Cellular from snail, has been solved (Brejc et al., 2001). The high Neurobiology affinity and specific interaction of ␣-BTX with AChR has Vrije Universiteit been of considerable importance in the study of the De Boelelaan 1087 ligand binding site of AChR. The ligand binding site of 1081 HV Amsterdam AChR is located mainly at the ␣ subunit, in the vicinity The Netherlands of Cys192 and Cys193 (Kao et al., 1984; Neumann et 6 Division of Molecular Carcinogenesis al., 1985), though residues in the interface of neighboring Netherlands Cancer Institute subunits contribute also to the binding site (Changeux Plesmanlaan 121 and Edelstein, 1998; Karlin and Akabas, 1995 and refer-1066 CX Amsterdam ences cited therein). Short synthetic peptides derived The Netherlands from this region of the AChR ␣ subunit were shown to bind ␣-BTX (Lentz, 1995; Neumann et al., 1986a). A 12mer synthetic peptide corresponding to residues 185-196 of the AChR, and encompassing the two tandem Summary cysteines, was found to bind agonists specifically and to inhibit the binding of ␣-BTX to AChR with an IC 50 of We have determined the crystal structure at 1.8 Å reso-10 Ϫ4 M (Neumann et al., 1986a, 1986b).
Molecular medicine (Cambridge, Mass.), Jan 4, 2015
Humanin and its derivatives are peptides known for their protective anti-apoptotic effects agains... more Humanin and its derivatives are peptides known for their protective anti-apoptotic effects against Alzheimer's disease. Herein, we identify a novel function of the humanin-derivative AGA(C8R)-HNG17-namely, protection against cellular necrosis. Necrosis is one of the main modes of cell death, which was until recently considered an unmoderated process. However, recent findings suggest the opposite. We have found that AGA(C8R)-HNG17 confers protection against necrosis in the neuronal cell lines PC-12 and NSC-34, where necrosis is induced in a glucose free medium by either chemohypoxia or by a shift from apoptosis to necrosis. Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect. This is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema as measured by MRI. An insight into the peptide's anti-necrotic mechanism was attained through...
Surface characterization and evaluation of biofilm growth on reverse osmosis membranes functional... more Surface characterization and evaluation of biofilm growth on reverse osmosis membranes functionalized with bio-active peptides Marina-Yamit Lutskiy1, Shani Avneri1, Roza Fainshtein1, Sophia Belfer1, Zeev Ronen2, Roni Kasher1 1Department of Desalination & Water Treatment and 2Department of Hydrology & Environmental Microbiology, Zuckerberg Institute for Water Research, The Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sde Boker 84990, Israel A major problem in reverse osmosis (RO) and nanofiltration (NF) technologies is fouling, and the most rigorous type of fouling is biofouling. In our recent study we have developed a novel approach to control biofouling of RO membranes which is based on multivalent linking of antimicrobial peptides (AMPs) to the membrane surface and inhibition of biofilm formation (Fig 1). Figure 1: Schematic illustration of bio-active peptides immobilized onto RO membranes through maleimide-thiol chemistry. Here we present a thorou...
Swelling of the active layer of reverse osmosis (RO) membranes has an important effect on permeat... more Swelling of the active layer of reverse osmosis (RO) membranes has an important effect on permeate water flux. The effects of organic- and biofouling on the swelling of the RO membrane active layer and the consequent changes of permeate flux are examined here. A cross-linked aromatic oligoamide film that mimics the surface chemistry of an RO polyamide membrane was synthesized stepwise on gold-coated surfaces. Foulant adsorption to the oligoamide film and its swelling were measured with a quartz crystal microbalance, and the effects of fouling on the membrane's performance were evaluated. The foulants were extracellular polymeric substances (EPS) extracted from fouled RO membranes and organic compounds of ultrafiltration permeate (UFP) from a membrane bioreactor used to treat municipal wastewater. The adsorbed foulants affected the swelling of the cross-linked oligoamide film differently. EPS had little effect on the swelling of the oligoamide film, whereas UFP significantly impaired swelling. Permeate flux declined more rapidly under UFP fouling than it did under EPS. Foulant adsorption was shown to diminish swelling of the aromatic oligoamide surfaces. Among the already known RO membrane fouling mechanisms, a novel RO fouling mechanism is proposed, in which foulant-membrane interactions hinder membrane swelling and thus increase hydraulic resistance.
Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine rec... more Alpha-bungarotoxin (alpha-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. In the following we review multi-phase research of the design, synthesis and structure analysis of peptides that bind alpha-BTX and inhibit its binding to AChR. Structure-based design concomitant with biological information of the alpha-BTX/AChR system yielded 13-mer peptides that bind to alpha-BTX with high affinity and are potent inhibitors of alpha-BTX binding to AChR (IC(50) of 2 nM). X-Ray and NMR spectroscopy reveal that the high-affinity peptides fold into an anti-parallel beta-hairpin structure when bound to alpha-BTX. The structures of the bound peptides and the homologous loop of acetylcholine binding protein, a soluble analog of AChR, are remarkably similar. Their superposition indicates that the toxin wraps around the binding-site loop, and in addition, binds tightly at the interface of tw...
Proceedings of the National Academy of Sciences, 2001
Snake-venom ␣-bungarotoxin is a member of the ␣-neurotoxin family that binds with very high affin... more Snake-venom ␣-bungarotoxin is a member of the ␣-neurotoxin family that binds with very high affinity to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. The structure of the complex between ␣-bungarotoxin and a 13-mer peptide (WRYYES-SLEPYPD) that binds the toxin with high affinity, thus inhibiting its interactions with AChR with an IC 50 of 2 nM, has been solved by 1 H-NMR spectroscopy. The bound peptide folds into a -hairpin structure created by two antiparallel -strands, which combine with the already existing triple-stranded -sheet of the toxin to form a five-stranded intermolecular, antiparallel -sheet. Peptide residues Y3 P , E5 P , and L8 P have the highest intermolecular contact area, indicating their importance in the binding of ␣-bungarotoxin; W1 P , R2 P , and Y4 P also contribute significantly to the binding. A large number of characteristic hydrogen bonds and electrostatic and hydrophobic interactions are observed in the complex. The high-affinity peptide exhibits inhibitory potency that is better than any known peptide derived from AChR, and is equal to that of the whole ␣-subunit of AChR. The high degree of sequence similarity between the peptide and various types of AChRs implies that the binding mode found within the complex might possibly mimic the receptor binding to the toxin. The design of the high-affinity peptide was based on our previous findings: (i) the detection of a lead peptide (MRYYES-SLKSYPD) that binds ␣-bungarotoxin, using a phage-display peptide library, (ii) the information about the three-dimensional structure of ␣-bungarotoxin͞lead-peptide complex, and (iii) the amino acid sequence analysis of different AChRs.
The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since it... more The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since its hydrophobic character hampers its successful 3 Department of Organic Chemistry crystallization. There have been several attempts to 4 Department of Immunology crystallize the extracellular domain of AChR ␣ subunit Weizmann Institute of Science and most recently, the X-ray structure of an acetylcho-Rehovot 76100 line binding protein (AChBP), a water-soluble homolog Israel of the nicotinic AChR ligand binding domain isolated 5 Department of Molecular and Cellular from snail, has been solved (Brejc et al., 2001). The high Neurobiology affinity and specific interaction of ␣-BTX with AChR has Vrije Universiteit been of considerable importance in the study of the De Boelelaan 1087 ligand binding site of AChR. The ligand binding site of 1081 HV Amsterdam AChR is located mainly at the ␣ subunit, in the vicinity The Netherlands of Cys192 and Cys193 (Kao et al., 1984; Neumann et 6 Division of Molecular Carcinogenesis al., 1985), though residues in the interface of neighboring Netherlands Cancer Institute subunits contribute also to the binding site (Changeux Plesmanlaan 121 and Edelstein, 1998; Karlin and Akabas, 1995 and refer-1066 CX Amsterdam ences cited therein). Short synthetic peptides derived The Netherlands from this region of the AChR ␣ subunit were shown to bind ␣-BTX (Lentz, 1995; Neumann et al., 1986a). A 12mer synthetic peptide corresponding to residues 185-196 of the AChR, and encompassing the two tandem Summary cysteines, was found to bind agonists specifically and to inhibit the binding of ␣-BTX to AChR with an IC 50 of We have determined the crystal structure at 1.8 Å reso-10 Ϫ4 M (Neumann et al., 1986a, 1986b).
We describe a novel approach to develop peptides with estrogen like activity using a monoclonal a... more We describe a novel approach to develop peptides with estrogen like activity using a monoclonal antibody specific to estradiol (mAb E2-15) for the affinity selection of phage displayed peptides from a combinatorial peptide library. Based on the sequences of the selected phage, we synthesized a 15-mer linear peptide LPALDPTKRWFFETK which was derivatized to a 23 mer cyclic peptide CAELPALDPT-KRWFFETKPPPPC. Both peptides displayed estrogen-like activity according to the following criteria:(i) in inhibiting the binding of [ 3 H]estradiol to mAb E2-15 and to estrogen receptor (ER)␣; (ii) in inducing transcriptional activity in MCF7 human breast cancer cells transfected with an estrogen receptor element luciferase construct and (iii) in causing an increase in creatine kinase specific activity in rat tissues in vivo. This approach can be employed to design peptide mimetic for other hormones as well.
Currently used antiestrogenic drugs against hormone-dependent breast cancer, and estrogenic drugs... more Currently used antiestrogenic drugs against hormone-dependent breast cancer, and estrogenic drugs used in treatment of osteoporosis, are associated with risk factors. Therefore, there is a strong need to develop selective estrogen receptor modulators with better tissue selectivity. In a recent study (Peptides, 2002, Vol. 3, 573-580), we used a monoclonal antibody to estradiol (mAb-E2) to screen a phage-display peptide library. We identified a 15-mer peptide (peptide H5) that recognizes mAb-E2 (IC 50 1 M) and estrogen receptor (ER)␣ (IC 50 500 M) but not ER, and displays estrogen-like activity in vitro and in vivo. In this study, we designed and prepared peptides based on peptide H5, which possess improved estrogenic activity, by evaluating their binding to mAb-E2 and to ERs. Initially, we determined the minimal binding sequence of peptide H5 capable of binding mAb-E2 and ER. Subsequently, systematic single-residue replacements of the minimal sequence, followed by multiple-residue replacements, yielded hexa-and heptapeptides with increased affinities to mAb-E2 and to ER. The most promising peptides, VSWFFE (EMP-1) and VSWFFED (EMP-2) (EMP: estrogen-mimetic peptide), bind mAb-E2 with high affinity (IC 50 of 6 and 30 nM, respectively), recognize ERs with increased affinity (IC 50 of 100 M for ER␣, and 100 -250 M for ER), and possess estrogenic activity in vivo. The short peptides described in this study may be used as potential lead compounds for developing new ER ligands.
Design and synthesis of peptides that bind α-bungarotoxin with high affinity and mimic the three-... more Design and synthesis of peptides that bind α-bungarotoxin with high affinity and mimic the three-dimensional structure of the binding-site of acetylcholine receptor ARTICLE in BIOPHYSICAL CHEMISTRY · FEBRUARY 2003 Impact Factor: 1.99 · Abstract a-Bungarotoxin (a-BTX) is a highly toxic snake neurotoxin that binds to acetylcholine receptor (AChR) at the neuromuscular junction, and is a potent inhibitor of this receptor. In the following we review multi-phase research of the design, synthesis and structure analysis of peptides that bind a-BTX and inhibit its binding to AChR. Structurebased design concomitant with biological information of the a-BTXyAChR system yielded 13-mer peptides that bind to a-BTX with high affinity and are potent inhibitors of a-BTX binding to AChR (IC of 2 nM). X-Ray and NMR 50 spectroscopy reveal that the high-affinity peptides fold into an anti-parallel b-hairpin structure when bound to a-BTX. The structures of the bound peptides and the homologous loop of acetylcholine binding protein, a soluble analog of AChR, are remarkably similar. Their superposition indicates that the toxin wraps around the binding-site loop, and in addition, binds tightly at the interface of two of the receptor subunits and blocks access of acetylcholine to its binding site. The procedure described in this article may serve as a paradigm for obtaining high-affinity peptides in biochemical systems that contain a ligand and a receptor molecule. ᮊ -binding protein ૾ The sad news about John Edsall's passing reached us soon after his death. We are sorry that he was not able to celebrate his 100th birthday with us, but hope that he was able to enjoy the manuscripts that were sent to him directly, and that this dedicatory volume will be a fitting tribute.
... We have therefore turned to ran-dom combinatorial libraries and employed phage-display peptid... more ... We have therefore turned to ran-dom combinatorial libraries and employed phage-display peptide libraries to select peptides that interact specifically with a ... 5. Neumann D, Gershoni GM, Fridkin M, Fuchs S. Antibodies to syn-thetic peptides as probes for the binding site on the a ...
Acta Crystallographica Section A Foundations of Crystallography, 2002
The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since it... more The X-ray structure of AChR has not yet been solved 2 Department of Biological Chemistry since its hydrophobic character hampers its successful 3 Department of Organic Chemistry crystallization. There have been several attempts to 4 Department of Immunology crystallize the extracellular domain of AChR ␣ subunit Weizmann Institute of Science and most recently, the X-ray structure of an acetylcho-Rehovot 76100 line binding protein (AChBP), a water-soluble homolog Israel of the nicotinic AChR ligand binding domain isolated 5 Department of Molecular and Cellular from snail, has been solved (Brejc et al., 2001). The high Neurobiology affinity and specific interaction of ␣-BTX with AChR has Vrije Universiteit been of considerable importance in the study of the De Boelelaan 1087 ligand binding site of AChR. The ligand binding site of 1081 HV Amsterdam AChR is located mainly at the ␣ subunit, in the vicinity The Netherlands of Cys192 and Cys193 (Kao et al., 1984; Neumann et 6 Division of Molecular Carcinogenesis al., 1985), though residues in the interface of neighboring Netherlands Cancer Institute subunits contribute also to the binding site (Changeux Plesmanlaan 121 and Edelstein, 1998; Karlin and Akabas, 1995 and refer-1066 CX Amsterdam ences cited therein). Short synthetic peptides derived The Netherlands from this region of the AChR ␣ subunit were shown to bind ␣-BTX (Lentz, 1995; Neumann et al., 1986a). A 12mer synthetic peptide corresponding to residues 185-196 of the AChR, and encompassing the two tandem Summary cysteines, was found to bind agonists specifically and to inhibit the binding of ␣-BTX to AChR with an IC 50 of We have determined the crystal structure at 1.8 Å reso-10 Ϫ4 M (Neumann et al., 1986a, 1986b).
Molecular medicine (Cambridge, Mass.), Jan 4, 2015
Humanin and its derivatives are peptides known for their protective anti-apoptotic effects agains... more Humanin and its derivatives are peptides known for their protective anti-apoptotic effects against Alzheimer's disease. Herein, we identify a novel function of the humanin-derivative AGA(C8R)-HNG17-namely, protection against cellular necrosis. Necrosis is one of the main modes of cell death, which was until recently considered an unmoderated process. However, recent findings suggest the opposite. We have found that AGA(C8R)-HNG17 confers protection against necrosis in the neuronal cell lines PC-12 and NSC-34, where necrosis is induced in a glucose free medium by either chemohypoxia or by a shift from apoptosis to necrosis. Our studies in traumatic brain injury models in mice, where necrosis is the main mode of neuronal cell death, have shown that AGA(C8R)-HNG17 has a protective effect. This is demonstrated by a decrease in a neuronal severity score and by a reduction in brain edema as measured by MRI. An insight into the peptide's anti-necrotic mechanism was attained through...
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