Meir Wilchek
Encyclopedia
Meir Wilchek is an Israeli biochemist.
He is a professor at the Weizmann Institute of Science
.
, Poland
, scion of a rabbinical family. During the Holocaust, he escaped from the German occupied territories to the territories occupied by Russia
, and was transferred to Siberia
, while his father, who served as a community rabbi in Warsaw was killed in Flossenbürg concentration camp
. He survived, and immigrated to Israel
in 1949 with his mother and sister. He graduated with B.Sc. in chemistry from Bar Ilan university and Ph. D. in biochemistry from the Weizmann Institute of Science
. Wilchek has published over 400 scientific papers, and consulted various biotech companies. He was also in the party list of Mafdal and Meimad
for the Knesset
.
, affinity label
ing, affinity therapy, and the avidin
-biotin
system. The Avidin-biotin complex is the highest affinity interaction in nature, and its utilization to biochemistry
integrates all of the former approaches.
Other contributions include conversion of serine
s to cysteine
s, and involvement with energy transfer studies between aromatic amino acids
chromophores, an approach known today as FRET
. He also studied the fine structure of these chromophores using circular dichroism
. More recently, he participated in a research team who studied how garlic
works at the molecular level, thanks to a unique biotechnological procedure for producing large quantities of pure allicin, garlic's main biologically active component.
is a method of separating biochemical mixtures, based on a highly specific biologic interaction such as that between antigen
and antibody
, enzyme
and substrate
, or receptor
and ligand
. The method was subsequently adopted for a variety of other techniques. Specific uses of affinity chromatography include antibody affinity, Immobilized metal ion affinity chromatography and purification of recombinant proteins - possibly the most common use of the method. To purify, proteins are tagged e.g. using His-tags or GST (glutathione-S-transferase) tags, which can be recognized by a metal ion ligand, such as imidazole
.
In 1971, Wilchek and colleagues applied this method to show that protein kinase
is composed of regulatory and catalytic subunits. In 1972, Wilchek showed that the method can be used to remove toxic compounds from blood, as exemplified by the removal of heme peptides from blood using immobilized human serum albumin, thus laying the grounds for modern hemoperfusion
is a molecule
that is similar in structure to a particular substrate
for a specific enzyme
. It is considered to be a class of irreversible inhibitors. These molecules covalently modify active site
residues in order to elucidate the structure of the active site. Using this method, Wilchek collaborated with a team who proved that the binding site
of antibodies lies in the Fv portion of the molecule and involves three hypervariable sites, today called the complementarity-determining regions (CDRs).
, Ester Hurwitz, and Ruth Arnon
. In 1975, they applied drug-conjugated antibodies for the targeted delivery of cytotoxic compounds to cancer cells. They also demonstrated the advantage of having a polymeric spacer between the antibody and the drug and showed the effectiveness of conjugating simple polymers such as dextran
for drug delivery and targeting. This approach was later adopted by others and eventually led to efficient treatment of human breast cancer
by recombinant humanized anti-HER2 antibody (Herceptin) in a mixture with paclitaxel
and doxorubicin
. In 2003, Wilchek collaborated in a team who introduced a system based on antibody-directed enzyme prodrug therapy (ADEPT
), using antibody-conjugated alliinase
to produce a cytotoxic agent, allicin, in situ (at the site) of the cancer
–biotin
system is a technique for studying the interaction between two biomolecules in an indirect manner, as follows: Biotin is chemically coupled to a binder molecule (e.g., a protein, DNA, hormone, etc.) without disturbing the interaction with its target molecule; avidin is then used to “sandwich” between the biotinylated
binder and a reporter molecule or probe. This allows for a variety of tasks, including localization and identification of the binder or target molecule. Consequently, the avidin-biotin system can frequently replace radioactive probes.
Together with Ed Bayer, Wilchek established the Avidin-biotin system as a powerful tool in biological sciences. Early in the 1970s, they exploited Avidin as a probe and developed new methods and reagents to biotinylate
antibodies and other biomolecules. Today, the system is applied in research and diagnostics as well as medical devices and pharmaceuticals. Examples include western blot
, ELISA
, ELISPOT
and pull-down assays.
More recently, Wilchek participated in structural studies of the avidin–biotin complex, to characterize the unique properties of this strong interaction. The studies have culminated in the determination of the 3D structure
of the avidin–biotin complex by X-ray crystallography, which aids in the design of specific artificial recognition sites.
He is a professor at the Weizmann Institute of Science
Weizmann Institute of Science
The Weizmann Institute of Science , known as Machon Weizmann, is a university and research institute in Rehovot, Israel. It differs from other Israeli universities in that it offers only graduate and post-graduate studies in the sciences....
.
Early life and education
Meir Wilchek was born in WarsawWarsaw
Warsaw is the capital and largest city of Poland. It is located on the Vistula River, roughly from the Baltic Sea and from the Carpathian Mountains. Its population in 2010 was estimated at 1,716,855 residents with a greater metropolitan area of 2,631,902 residents, making Warsaw the 10th most...
, Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
, scion of a rabbinical family. During the Holocaust, he escaped from the German occupied territories to the territories occupied by Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
, and was transferred to Siberia
Siberia
Siberia is an extensive region constituting almost all of Northern Asia. Comprising the central and eastern portion of the Russian Federation, it was part of the Soviet Union from its beginning, as its predecessor states, the Tsardom of Russia and the Russian Empire, conquered it during the 16th...
, while his father, who served as a community rabbi in Warsaw was killed in Flossenbürg concentration camp
Flossenbürg concentration camp
Konzentrationslager Flossenbürg was a Nazi concentration camp built in May 1938 by the Schutzstaffel Economic-Administrative Main Office at Flossenbürg, in the Oberpfalz region of Bavaria, Germany, near the border with Czechoslovakia. Until its liberation in April 1945, more than 96,000 prisoners...
. He survived, and immigrated to Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
in 1949 with his mother and sister. He graduated with B.Sc. in chemistry from Bar Ilan university and Ph. D. in biochemistry from the Weizmann Institute of Science
Weizmann Institute of Science
The Weizmann Institute of Science , known as Machon Weizmann, is a university and research institute in Rehovot, Israel. It differs from other Israeli universities in that it offers only graduate and post-graduate studies in the sciences....
. Wilchek has published over 400 scientific papers, and consulted various biotech companies. He was also in the party list of Mafdal and Meimad
Meimad
Meimad is a left-wing religious Zionist political party in Israel. Founded in 1999, it is based on the ideology of the Meimad movement founded in 1988 by Rabbi Yehuda Amital. At the national level, it was in alliance with the Labour Party, and until the 2006 elections, received 10th spot on the...
for the Knesset
Knesset
The Knesset is the unicameral legislature of Israel, located in Givat Ram, Jerusalem.-Role in Israeli Government :The legislative branch of the Israeli government, the Knesset passes all laws, elects the President and Prime Minister , approves the cabinet, and supervises the work of the government...
.
Scientific contributions
Meir Wilchek is known for his research in the field of biorecognition or affinity phenomenon, and its various application, e.g. for affinity chromatographyAffinity chromatography
Affinity chromatography is a method of separating biochemical mixtures and based on a highly specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligand.-Uses:Affinity chromatography can be used to:...
, affinity label
Affinity label
Affinity label is a molecule that is similar in structure to a particular substrate for a specific enzyme. It is considered to be a class of enzyme inactivators. These molecules covalently modify active site residues in order to elucidate the structure of the active site.These types of compounds...
ing, affinity therapy, and the avidin
Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...
-biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
system. The Avidin-biotin complex is the highest affinity interaction in nature, and its utilization to biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
integrates all of the former approaches.
Other contributions include conversion of serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
s to cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s, and involvement with energy transfer studies between aromatic amino acids
Aromatic amino acids
Aromatic amino acids are amino acids that include an aromatic ring.Examples include:* Among 20 standard amino acids: phenylalanine, tryptophan, and tyrosine* Others: thyroxine-See also:* Aromatic L-amino acid decarboxylase...
chromophores, an approach known today as FRET
Fret
A fret is a raised portion on the neck of a stringed instrument, that extends generally across the full width of the neck. On most modern western instruments, frets are metal strips inserted into the fingerboard...
. He also studied the fine structure of these chromophores using circular dichroism
Circular dichroism
Circular dichroism refers to the differential absorption of left and right circularly polarized light. This phenomenon was discovered by Jean-Baptiste Biot, Augustin Fresnel, and Aimé Cotton in the first half of the 19th century. It is exhibited in the absorption bands of optically active chiral...
. More recently, he participated in a research team who studied how garlic
Garlic
Allium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
works at the molecular level, thanks to a unique biotechnological procedure for producing large quantities of pure allicin, garlic's main biologically active component.
Affinity chromatography
Affinity chromatographyAffinity chromatography
Affinity chromatography is a method of separating biochemical mixtures and based on a highly specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligand.-Uses:Affinity chromatography can be used to:...
is a method of separating biochemical mixtures, based on a highly specific biologic interaction such as that between antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
and antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
and substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
, or receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
and ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
. The method was subsequently adopted for a variety of other techniques. Specific uses of affinity chromatography include antibody affinity, Immobilized metal ion affinity chromatography and purification of recombinant proteins - possibly the most common use of the method. To purify, proteins are tagged e.g. using His-tags or GST (glutathione-S-transferase) tags, which can be recognized by a metal ion ligand, such as imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
.
In 1971, Wilchek and colleagues applied this method to show that protein kinase
Protein kinase
A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...
is composed of regulatory and catalytic subunits. In 1972, Wilchek showed that the method can be used to remove toxic compounds from blood, as exemplified by the removal of heme peptides from blood using immobilized human serum albumin, thus laying the grounds for modern hemoperfusion
Hemoperfusion
Hemoperfusion is a medical process used to remove toxic substances from a patient's blood. The technique involves passing large volumes of blood over an adsorbent substance. The adsorbent substance most commonly used in hemoperfusion are resins and activated carbon...
Affinity labeling
Affinity labelAffinity label
Affinity label is a molecule that is similar in structure to a particular substrate for a specific enzyme. It is considered to be a class of enzyme inactivators. These molecules covalently modify active site residues in order to elucidate the structure of the active site.These types of compounds...
is a molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
that is similar in structure to a particular substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
for a specific enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
. It is considered to be a class of irreversible inhibitors. These molecules covalently modify active site
Active site
In biology the active site is part of an enzyme where substrates bind and undergo a chemical reaction. The majority of enzymes are proteins but RNA enzymes called ribozymes also exist. The active site of an enzyme is usually found in a cleft or pocket that is lined by amino acid residues that...
residues in order to elucidate the structure of the active site. Using this method, Wilchek collaborated with a team who proved that the binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
of antibodies lies in the Fv portion of the molecule and involves three hypervariable sites, today called the complementarity-determining regions (CDRs).
Affinity therapy
Affinity therapy, or immunotoxins is a biorecognition-based approach to selectively deliver a cytotoxic drug or toxin to a specific target cell. The field of affinity therapy was pioneered by Wilchek, together with Michael SelaMichael Sela
Michael Sela is an Israeli immunologist of Polish Jewish origin. He is W. Garfield Weston Professor of Immunology at the Weizmann Institute of Science in Rehovot.- Birth and academic career :...
, Ester Hurwitz, and Ruth Arnon
Ruth Arnon
Ruth Arnon is an Israeli biochemist and codeveloper of the multiple sclerosis drug Copaxone. She is currently the Paul Ehrlich Professor of Immunology at the Weizmann Institute of Science.-Early life:...
. In 1975, they applied drug-conjugated antibodies for the targeted delivery of cytotoxic compounds to cancer cells. They also demonstrated the advantage of having a polymeric spacer between the antibody and the drug and showed the effectiveness of conjugating simple polymers such as dextran
Dextran
Dextran is a complex, branched glucan composed of chains of varying lengths...
for drug delivery and targeting. This approach was later adopted by others and eventually led to efficient treatment of human breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
by recombinant humanized anti-HER2 antibody (Herceptin) in a mixture with paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
and doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
. In 2003, Wilchek collaborated in a team who introduced a system based on antibody-directed enzyme prodrug therapy (ADEPT
ADEPT
ADEPT is a strategy to overcome the problems of lack of tumor selectivity. An antibody designed/developed against a tumor antigen is linked to an enzyme and injected to the blood, resulting in selective binding of the enzyme in the tumor...
), using antibody-conjugated alliinase
Alliinase
In enzymology, an alliin lyase is an enzyme that catalyzes the chemical reactionHence, this enzyme has one substrate, S-alkyl-L-cysteine S-oxide, and two products, alkyl sulfenate and 2-aminoacrylate....
to produce a cytotoxic agent, allicin, in situ (at the site) of the cancer
The avidin-biotin system
The avidinAvidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...
–biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
system is a technique for studying the interaction between two biomolecules in an indirect manner, as follows: Biotin is chemically coupled to a binder molecule (e.g., a protein, DNA, hormone, etc.) without disturbing the interaction with its target molecule; avidin is then used to “sandwich” between the biotinylated
Biotinylation
In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...
binder and a reporter molecule or probe. This allows for a variety of tasks, including localization and identification of the binder or target molecule. Consequently, the avidin-biotin system can frequently replace radioactive probes.
Together with Ed Bayer, Wilchek established the Avidin-biotin system as a powerful tool in biological sciences. Early in the 1970s, they exploited Avidin as a probe and developed new methods and reagents to biotinylate
Biotinylation
In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...
antibodies and other biomolecules. Today, the system is applied in research and diagnostics as well as medical devices and pharmaceuticals. Examples include western blot
Western blot
The western blot is a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native proteins by 3-D structure or denatured proteins by the length of the polypeptide...
, ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
, ELISPOT
ELISPOT
The Enzyme-linked immunosorbent spot assay is a common method for monitoring immune responses in humans and animals. It was developed by Cecil Czerkinsky in 1983....
and pull-down assays.
More recently, Wilchek participated in structural studies of the avidin–biotin complex, to characterize the unique properties of this strong interaction. The studies have culminated in the determination of the 3D structure
Quaternary structure
In biochemistry, quaternary structure is the arrangement of multiple folded protein or coiling protein molecules in a multi-subunit complex.-Description and examples:...
of the avidin–biotin complex by X-ray crystallography, which aids in the design of specific artificial recognition sites.
Honors and awards
- 1981-1982 Fogarty International Scholar
- 1981 Honorary Member of the American Society of Biological Chemistry
- 1984 Rothschild Prize in Chemistry
- 1987 Wolf Prize in MedicineWolf Prize in MedicineThe Wolf Prize in Medicine is awarded once a year by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The Prize is probably the third most prestigious award...
, jointly with Pedro CuatrecasasPedro CuatrecasasPedro Cuatrecasas is an American biochemist and an Adjunct Professor of Pharmacology & Medicine at the University of California, San Diego.- Birth and education :...
, "for the invention and development of affinity chromatographyAffinity chromatographyAffinity chromatography is a method of separating biochemical mixtures and based on a highly specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor and ligand.-Uses:Affinity chromatography can be used to:...
and its applications to biomedical sciences." - 1987 Pierce Prize for Biorecognition Technology
- 1988 Elected Member of the Israel Academy of Sciences and HumanitiesIsrael Academy of Sciences and HumanitiesThe Israel Academy of Sciences and Humanities, based in Jerusalem, was set up in 1961 by the State of Israel to foster contact between scholars from the sciences and humanities in Israel, to advise the government on research projects of national importance, and to promote excellence. It comprises...
- 1989 Doctor of Science, honoris causa, University of Waterloo, Canada
- 1989 Barnett Lecturer, Northeastern University, Boston
- 1990 Israel PrizeIsrael PrizeThe Israel Prize is an award handed out by the State of Israel and is largely regarded as the state's highest honor. It is presented annually, on Israeli Independence Day, in a state ceremony in Jerusalem, in the presence of the President, the Prime Minister, the Knesset chairperson, and the...
, in life sciences - 1990 Sarstedt Prize (Numbrecht, Germany)
- 1993 Foreign Associate Member, Institute of MedicineInstitute of MedicineThe Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
, National Academy of Science, USA - 1995 Doctor of Science, honoris causa, Bar Ilan Iniversity, Israel
- 1996 International Distinguished Clinical Chemist Award, International Federation of Clinical ChemistryInternational Federation of Clinical Chemistry and Laboratory MedicineThe International Federation of Clinical Chemistry and Laboratory Medicine or IFCC was founded in 1952 to promote a global vision of Clinical Chemistry & Laboratory Medicine worldwide and to be the leading organization in the field...
(IFCC) - 2000 Doctor of Science, honoris causa, University Jyvaskyla, Finland
- 2000 Honorary Doctorate, Ben-Gurion University of the Negev
- 2002 Honorary Citizen, City of RehovotRehovotRehovot is a city in the Center District of Israel, about south of Tel Aviv. According to the Israel Central Bureau of Statistics , at the end of 2009 the city had a total population of 112,700. Rehovot's official website estimates the population at 114,000.Rehovot was built on the site of Doron,...
, Israel - 2004 Christian B. Anfinsen Award of The Protein Society
- 2004 Wilhelm-Exner Medal, OGV, President of Austria
- 2005 Emet Prize, presented by the Prime Minister of Israel
External links
See also
- List of Israel Prize recipients