tanya sanders | Brown University (original) (raw)
Papers by tanya sanders
Journal of The American Chemical Society, 1997
... Jeffrey L. Conroy, Tanya C. Sanders, and Christopher T. Seto*. Contribution from the Departme... more ... Jeffrey L. Conroy, Tanya C. Sanders, and Christopher T. Seto*. Contribution from the Department of Chemistry, Brown University, Providence, Rhode Island 02912. J. Am. Chem. Soc. , 1997, 119 (18), pp 42854291. DOI: 10.1021 ...
Organic Letters, 1999
[formula: see text] Aminocyclodextrins are known to bind phosphate esters such as phosphotyrosine... more [formula: see text] Aminocyclodextrins are known to bind phosphate esters such as phosphotyrosine and p-nitrophenyl phosphate. This paper describes the inhibition of phosphate ester hydrolysis, as catalyzed by lambda-protein phosphatase and acid phosphatase, that is caused by such binding interactions. ROESY studies provide structural information about the cyclodextrin-aryl phosphate complexes. In addition, these experiments are used to generate approximations of the rates of dissociation of the noncovalent complexes.
Acta Biochimica Et Biophysica Sinica, 2010
a-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonist... more a-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two a-conotoxins, Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus leopardus. Both of them have the typical 4/7-type framework of the subfamily of a-conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized these two toxins and characterized their functional properties. The synthetic Mr1.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in the oocyte-expressed rat a7 nAChR, whereas Lp1.4 was an unexpected specific blocker of the mouse fetal muscle a1b1gd receptor. Although their inhibition affinities were relatively low, their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo, suggesting that it should be further investigated with respect to its molecular role in analgesia and its mechanism or therapeutic target for the treatment of pain.
Peptides, 2008
Cone snails comprise approximately 700 species of venomous molluscs which have evolved the abilit... more Cone snails comprise approximately 700 species of venomous molluscs which have evolved the ability to generate multiple toxins with varied and exquisite selectivity. alpha-Conotoxin is a powerful tool for defining the composition and function of nicotinic acetylcholine receptors which play a crucial role in excitatory neurotransmission and are important targets for drugs and insecticides. An alpha4/7 conotoxin, Lp1.1, originally identified by cDNA and genomic DNA cloning from Conus leopardus, was found devoid of the highly conserved Pro residue in the first intercysteine loop. To further study this toxin, alpha-Lp1.1 was chemically synthesized and refolded into its globular disulfide isomer. The synthetic Lp1.1 induced seizure and paralysis on freshwater goldfish and selectively reversibly inhibited ACh-evoked currents in Xenopus oocytes expressing rat alpha3beta2 and alpha6alpha3beta2 nAChRs. Comparing the distinct primary structure with other functionally related alpha-conotoxins could indicate structural features in Lp1.1 that may be associated with its unique receptor recognition profile.
European Journal of Neuroscience, 2009
We report here the construction of a novel knock-in mouse expressing chimeric α3 nicotinic acetyl... more We report here the construction of a novel knock-in mouse expressing chimeric α3 nicotinic acetylcholine receptor (nAChR) subunits with pharmacological sensitivity to α-bungarotoxin (αBTX). Sensitivity was generated by substituting five amino acids in the loop C (β9–β10) region of the mouse α3 subunit with the corresponding residues from the α1 subunit of the muscle type receptor from Torpedo californica. To demonstrate the utility of the underlying concept, expressed α3[5] subunits were characterized in the superior cervical ganglia (SCG) of homozygous knock-in mice, where the synaptic architecture of postsynaptic α3-containing nAChR clusters could now, for the first time, be directly visualized and interrogated by live-staining with rhodamine-conjugated αBTX. Consistent with the postsynaptic localization of ganglionic nAChRs, the αBTX-labeled puncta colocalized with a marker for synaptic varicosities. Following in vivo deafferentation, these puncta persisted but with significant changes in intensity and distribution that varied with the length of the recovery period. Compound action potentials and excitatory postsynaptic potentials recorded from SCG of mice homozygous for α3[5] were abolished by 100 nmαBTX, even in an α7 null background, demonstrating that synaptic throughput in the SCG is completely dependent on the α3-subunit. In addition, we observed that the genetic background of various inbred and outbred mouse lines greatly affects the functional expression of α3[5]-nAChRs, suggesting a powerful new approach for exploring the molecular mechanisms underlying receptor assembly and trafficking. As αBTX-sensitive sequences can be readily introduced into other nicotinic receptor subunits normally insensitive to αBTX, the findings described here should be applicable to many other receptors.
Journal of Organic Chemistry, 1993
Page 1. 5598 J. Org. Chem. 1993,58, 5598-5599 A Regiospecific Fluorination Strategy: Synthesis of... more Page 1. 5598 J. Org. Chem. 1993,58, 5598-5599 A Regiospecific Fluorination Strategy: Synthesis of (a-Fluoropropargy1)- and (a-Fluoroally1)phosphonate Esters Tanya C. Sanders, and Gerald B. Hammond' Department of Chemistry ...
Journal of Fluorine Chemistry, 1997
Horner-Wadsworth-Emmons condensation of (α-fluoropropargyl) phosphonate ester 3 and p-anisaldehyd... more Horner-Wadsworth-Emmons condensation of (α-fluoropropargyl) phosphonate ester 3 and p-anisaldehyde provides a new method for the synthesis of monofluoro-conjugated enynes. Spontaneous crystallization of 4 yielded the Zisomer of 2-fiuoro-1-(p-methoxyphenyl)-1-penten- 3-yne. A comparison of bond angles and distances between 4 and vinylacetylene showed shorter bond distances along the enyne system in 4.
Journal of Organic Chemistry, 1996
Journal of The American Chemical Society, 1997
... Jeffrey L. Conroy, Tanya C. Sanders, and Christopher T. Seto*. Contribution from the Departme... more ... Jeffrey L. Conroy, Tanya C. Sanders, and Christopher T. Seto*. Contribution from the Department of Chemistry, Brown University, Providence, Rhode Island 02912. J. Am. Chem. Soc. , 1997, 119 (18), pp 42854291. DOI: 10.1021 ...
Organic Letters, 1999
[formula: see text] Aminocyclodextrins are known to bind phosphate esters such as phosphotyrosine... more [formula: see text] Aminocyclodextrins are known to bind phosphate esters such as phosphotyrosine and p-nitrophenyl phosphate. This paper describes the inhibition of phosphate ester hydrolysis, as catalyzed by lambda-protein phosphatase and acid phosphatase, that is caused by such binding interactions. ROESY studies provide structural information about the cyclodextrin-aryl phosphate complexes. In addition, these experiments are used to generate approximations of the rates of dissociation of the noncovalent complexes.
Acta Biochimica Et Biophysica Sinica, 2010
a-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonist... more a-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two a-conotoxins, Mr1.1 from the molluscivorous Conus marmoreus and Lp1.4 from the vermivorous Conus leopardus. Both of them have the typical 4/7-type framework of the subfamily of a-conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized these two toxins and characterized their functional properties. The synthetic Mr1.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in the oocyte-expressed rat a7 nAChR, whereas Lp1.4 was an unexpected specific blocker of the mouse fetal muscle a1b1gd receptor. Although their inhibition affinities were relatively low, their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo, suggesting that it should be further investigated with respect to its molecular role in analgesia and its mechanism or therapeutic target for the treatment of pain.
Peptides, 2008
Cone snails comprise approximately 700 species of venomous molluscs which have evolved the abilit... more Cone snails comprise approximately 700 species of venomous molluscs which have evolved the ability to generate multiple toxins with varied and exquisite selectivity. alpha-Conotoxin is a powerful tool for defining the composition and function of nicotinic acetylcholine receptors which play a crucial role in excitatory neurotransmission and are important targets for drugs and insecticides. An alpha4/7 conotoxin, Lp1.1, originally identified by cDNA and genomic DNA cloning from Conus leopardus, was found devoid of the highly conserved Pro residue in the first intercysteine loop. To further study this toxin, alpha-Lp1.1 was chemically synthesized and refolded into its globular disulfide isomer. The synthetic Lp1.1 induced seizure and paralysis on freshwater goldfish and selectively reversibly inhibited ACh-evoked currents in Xenopus oocytes expressing rat alpha3beta2 and alpha6alpha3beta2 nAChRs. Comparing the distinct primary structure with other functionally related alpha-conotoxins could indicate structural features in Lp1.1 that may be associated with its unique receptor recognition profile.
European Journal of Neuroscience, 2009
We report here the construction of a novel knock-in mouse expressing chimeric α3 nicotinic acetyl... more We report here the construction of a novel knock-in mouse expressing chimeric α3 nicotinic acetylcholine receptor (nAChR) subunits with pharmacological sensitivity to α-bungarotoxin (αBTX). Sensitivity was generated by substituting five amino acids in the loop C (β9–β10) region of the mouse α3 subunit with the corresponding residues from the α1 subunit of the muscle type receptor from Torpedo californica. To demonstrate the utility of the underlying concept, expressed α3[5] subunits were characterized in the superior cervical ganglia (SCG) of homozygous knock-in mice, where the synaptic architecture of postsynaptic α3-containing nAChR clusters could now, for the first time, be directly visualized and interrogated by live-staining with rhodamine-conjugated αBTX. Consistent with the postsynaptic localization of ganglionic nAChRs, the αBTX-labeled puncta colocalized with a marker for synaptic varicosities. Following in vivo deafferentation, these puncta persisted but with significant changes in intensity and distribution that varied with the length of the recovery period. Compound action potentials and excitatory postsynaptic potentials recorded from SCG of mice homozygous for α3[5] were abolished by 100 nmαBTX, even in an α7 null background, demonstrating that synaptic throughput in the SCG is completely dependent on the α3-subunit. In addition, we observed that the genetic background of various inbred and outbred mouse lines greatly affects the functional expression of α3[5]-nAChRs, suggesting a powerful new approach for exploring the molecular mechanisms underlying receptor assembly and trafficking. As αBTX-sensitive sequences can be readily introduced into other nicotinic receptor subunits normally insensitive to αBTX, the findings described here should be applicable to many other receptors.
Journal of Organic Chemistry, 1993
Page 1. 5598 J. Org. Chem. 1993,58, 5598-5599 A Regiospecific Fluorination Strategy: Synthesis of... more Page 1. 5598 J. Org. Chem. 1993,58, 5598-5599 A Regiospecific Fluorination Strategy: Synthesis of (a-Fluoropropargy1)- and (a-Fluoroally1)phosphonate Esters Tanya C. Sanders, and Gerald B. Hammond' Department of Chemistry ...
Journal of Fluorine Chemistry, 1997
Horner-Wadsworth-Emmons condensation of (α-fluoropropargyl) phosphonate ester 3 and p-anisaldehyd... more Horner-Wadsworth-Emmons condensation of (α-fluoropropargyl) phosphonate ester 3 and p-anisaldehyde provides a new method for the synthesis of monofluoro-conjugated enynes. Spontaneous crystallization of 4 yielded the Zisomer of 2-fiuoro-1-(p-methoxyphenyl)-1-penten- 3-yne. A comparison of bond angles and distances between 4 and vinylacetylene showed shorter bond distances along the enyne system in 4.
Journal of Organic Chemistry, 1996