The invention relates to heparinase III and mutants thereof. Modified forms of heparinase III having reduced enzymatic activity which are useful for a variety of purposes, including sequencing of heparin-like glycosaminoglycans (HLGAGs), removing active heparan sulfate from a solution, inhibition of
The invention relates to heparinase III and mutants thereof. Modified forms of heparinase III having reduced enzymatic activity which are useful for a variety of purposes, including sequencing of heparin-like glycosaminoglycans (HLGAGs), removing active heparan sulfate from a solution, inhibition of angiogenesis, etc. have been discovered according to the invention. The invention in other aspects relates to methods of treating cancer and inhibiting tumor cell growth and/or metastasis using heparinase III, or products produced by enzymatic cleavage by heparinase III of HLGAGs.
대표청구항▼
1. A substantially pure heparinase III, comprising:a polypeptide having the amino acid sequence of the mature peptide of SEQ ID NO: 2, wherein at least one histidine residue selected from the group consisting of His 36, His105, His110, His139, His152, His225, His234, His241, His424, His469, and His5
1. A substantially pure heparinase III, comprising:a polypeptide having the amino acid sequence of the mature peptide of SEQ ID NO: 2, wherein at least one histidine residue selected from the group consisting of His 36, His105, His110, His139, His152, His225, His234, His241, His424, His469, and His539 has been substituted with a residue selected from the group consisting of alanine, serine, tyrosine, threonine, and lysine. 2. A substantially pure heparinase III comprising:a modified heparinase III having a modified product profile, wherein the modified product profile of the modified heparinase III is at least 10% different than a native product profile of a native heparinase III, wherein the substantially pure heparinase III has the amino acid sequence of the mature peptide of SEQ ID NO: 2 where at least one histidine residue selected from the group consisting of His 36, His105, His110, His139, His152, His225, His234, His241, His424, His469, and His539 has been substituted with a residue selected from the group consisting of alanine, serine, tyrosine, threonine, and lysine. 3. A substantially pure heparinase III comprising:a modified heparinase III that can cleave a heparan sulfate substrate having modified heparinase III kcat value, wherein the modified heparinase III kcat value is at leas 10% different than a native heparinase III kcat value, wherein the substantially pure heparinase III has the amino acid sequence of the mature peptide of SEQ ID NO: 2 where at least one histidine residue selected from the group consisting of His 36, His105, His110, His139, His152, His225, His234, His241, His424, His469, and His539 has been substituted with a residue selected from the group consisting o alanine, serine, tyrosine, threonine, and lysine. 4. A pharmaceutical preparation comprising a sterile formulation of the substantially pure heparinase III of claim 1 and a pharmaceutically acceptable carrier.5. An immobilized substantially pure modified heparinase III comprising:a modified heparinase III as in claim 1, and a solid support, wherein the modified heparinase III is immobilized on the solid support. 6. The substantially pure heparinase III of claim 1, wherein the polypeptide has at least one substitution within a histidine residue selected from the group consisting of His 110, His225, and His241.7. The substantially pure heparinase III of claim 1, wherein the polypeptide has a substitution at His110.8. The substantially pure heparinase III of claim 1, wherein the polypeptide has a substitution at His241.9. The substantially pure heparinase III of claim 1, wherein the polypeptide has a substitution at His225.10. The substantially pure heparinase III of claim 9, wherein the His225 is substituted with alanine.
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Venkataraman Ganesh (Somerville MA) Sasisekharan Viswanathan (Somerville MA) Sasisekharan Ram (Somerville MA) Bobba Ratnaleela (Somerville MA) Cooney Charles L. (Brookline MA) Langer Robert (Newton M, Computer-implemented process and computer system for estimating the three-dimensional shape of a ring-shaped molecule an.
Findlay Valerie S. (Horsham) Kerry Roger (Horsham) Pay Graham F. (Patcham) Wallis Robert B. (Leechponds Hills) Butler Keith D. (Soreham-by-Sea GB2), Heparin and hirudin antidotal compositions and methods.
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Langer Robert S. (Somerville MA) Linhardt Robert J. (Somerville MA) Cooney Charles L. (Brookline MA) Fitzgerald Gerald (York PA) Grant Arthur (Newton MA), Heparinase derived anticoagulants.
Zimmermann Joseph J. (Elm Grove WI) Lewis N. Tracey (Brossard CAX) Heft Robert A. (Ville St. Laurent CAX), Heparinase free of an anticoagulant component from flavobacterium Heparinum.
Morikawa Kiyoshi (Hinode JPX) Miyazono Hirofumi (Higashiyamato JPX) Maruyama Hiroshi (Higashiyamato JPX) Yoshida Keiichi (Higashimurayama JPX), Heparitinase, process for producing the same and bacteria producing the same.
Zimmerman Joseph J. (Boston MA) Cooney Charles L. (Brookline MA), Large scale method for purification of high purity heparinase from flavobacterium heparinum.
Foley Kevin M. (Franklin OH) Griffin Charles C. (Oxford OH) Amaya Eduardo (Monroe OH), Low molecular weight heparin derivatives having improved anti-Xa specificity.
Griffin Charles C. (710 Melissa Dr. Oxford OH 45056) Foley Kevin M. (5757 Lynn St. Franklin OH 45005) Amaya Eduardo (811 Sands Ave. Monroe OH 45050), Low molecular weight heparin derivatives with improved permeability.
Lormeau Jean-Claude (Maromme FRX) Petitou Maurice (Paris Cedex FRX) Choay Jean (Paris FRX), Low molecular weight heparins of regular structure, their preparation and their biological uses..
Sasisekharan Ramnath (Arlington MA) Moses Marsha A. (Brookline MA) Nugent Matthew A. (Bedford MA) Cooney Charles L. (Brookline MA) Langer Robert S. (Newton MA), Method for inhibiting angiogenesis using heparinase.
Zimmermann Joseph J. (Elm Grove WI) Lewis N. Tracey (Brossard CAX) Heft Robert A. (Ville St. Laurent CAX), Method for the enzymatic neutralization of heparin.
Skubitz Amy P. N. ; Furcht Leo T. ; Balles Mark ; Gregerson Dale S. ; Agarwal Anita ; Wright Martha M. ; Murali Shobana, Method for treating conditions of the eye using polypeptides.
Van Gorp Cornelius L. (Lebanon OH) Wolf Thomas M. (West Chester OH), Method for tumor regression in rats, mice and hamsters using hexuronyl hexosaminoglycan-containing compositions.
Toback F. Gary (Chicago IL) Lieske John C. (Evanston IL), Methods and compositions for detecting and treating kidney diseases associated with adhesion of crystals to kidney cells.
Biemann Klaus (Alton Bay NH) Juhasz Peter (Everett MA), Methods and products for mass spectrometric molecular weight determination of polyionic analytes employing polyionic rea.
Friedman Jeffrey M. ; Zhang Yiying ; Proenca Ricardo, Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof.
Su Hongsheng (Longueuil CAX) Blain Francoise (Mtl. CAX) Bennett Clark (Pierrefonds CAX) Gu Kangfu (D.D.O. CAX) Zimmermann Joseph (Elm Grove WI) Musil Roy (Carlsbad CA), Nucleic acid sequences and expression systems for heparinase II and heparinase III derived from Flavobacterium hepari.
Su Hongsheng,CAX ; Blain Francoise,CAX ; Bennett Clark,CAX ; Gu Kangfu,CAX ; Zimmermann Joseph ; Musil Roy, Nucleic acid sequences and expression systems for heparinase II and heparinase III derived from Flavobacterium heparinum.
Pecker Iris,ILX ; Vlodavsky Israel,ILX ; Feinstein Elena,ILX, Polynucleotide encoding a polypeptide having heparanase activity and expression of same in transduced cells.
Langer Robert S. (Cambridge MA) Linhardt Robert (Somerville MA) Cooney Charles L. (Brookline MA) Galliher Parrish M. (West Newton MA) Flanagan Margaret M. (Somerset MA) Klein Michael D. (Ann Arbor MI, Process for neutralizing heparin.
Langer ; Jr. Robert S. (Cambridge MA) Linhardt Robert (Somerville MA) Cooney Charles L. (Brookline MA) Galliher Parrish M. (West Newton MA), Process for producing heparinase.
Langer ; Jr. Robert S. (Cambridge MA) Linhardt Robert (Somerville MA) Cooney Charles L. (Brookline MA) Galliher Parrish M. (West Newton MA), Process for producing heparinase.
Nielsen Jorgen I. (Farum DKX), Process of using light absorption to control enzymatic depolymerization of heparin to produce low molecular weight hepar.
Hirsh Jack,CAX ; Shaklee Patrick N. ; Knobloch James E. ; Weitz Jeffrey I.,CAX ; Young Edward,CAX, Processes for the preparation of low-affinity, low molecular weight heparins useful as antithrombotics.
Sasisekharan Ramnath (Arlington MA) Lohse Daniel L. (Bryan TX) Cooney Charles L. (Brookline MA) Linhardt Robert J. (Iowa City IA) Langer Robert S. (Newton MA), Purification of heparinase I, II, and III from Flavobacterium heparinum.
Sasisekharan Ramnath (Arlington MA) Lohse Daniel L. (Bryan TX) Cooney Charles L. (Brookline MA) Linhardt Robert J. (Iowa City IA) Langer Robert S. (Newton MA), Purification, composition and specificity of heparinase I, II, and III from flavobacterium heparinum.
Branellec Jean-Franois (Mont Saint Aignan FRX) Espejo Jose (Bois Guillaume FRX) Picart Philippe (Rouen FRX), Purified heparin fractions, method for obtaining them and pharmaceutical compositions containing them.
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Lakowicz Joseph R. ; Burke Thomas G. ; Gryczynski Ignacy ; Malak Henryk, Two-photon and multi-photon measurement of analytes in animal and human tissues and fluids.
Liu,Dongfang; Pojasek,Kevin; Shriver,Zachary; Holley,Kristine; El Shabrawi,Yosuf; Venkataraman,Ganesh; Sasisekharan,Ram, Heparinase III and methods of specifically cleaving therewith.
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Chandrasekaran, Aarthi; Sengupta, Shiladitya; Berry, David A.; Holley, Kristine; Zhao, Ganlin; Sasisekharan, Ram, Methods and compositions related to the modulation of intercellular junctions.
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Liu,Dongfang; Pojasek,Kevin; Shriver,Zachary; Holley,Kristine; El Shabrawi,Yosuf; Venkataraman,Ganesh; Sasisekharan,Ram, Methods for preparing low molecular weight heparin with modified heparinase III.
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