Meir Wilchek (; born 17 October 1935) is an Israeli biochemist. He is a professor at the

Weizmann Institute of Science The Weizmann Institute of Science ( ''Machon Weizmann LeMada'') is a Public university, public research university in Rehovot, Israel, established in 1934, fourteen years before the State of Israel was founded. Unlike other List of Israeli uni ...

Early life and education

Meir Wilchek was born in

Warsaw Warsaw, officially the Capital City of Warsaw, is the capital and List of cities and towns in Poland, largest city of Poland. The metropolis stands on the Vistula, River Vistula in east-central Poland. Its population is officially estimated at ...

, Poland, scion of a rabbinical family. During the

Holocaust The Holocaust (), known in Hebrew language, Hebrew as the (), was the genocide of History of the Jews in Europe, European Jews during World War II. From 1941 to 1945, Nazi Germany and Collaboration with Nazi Germany and Fascist Italy ...

, he escaped from the German-occupied territories to the territories occupied by Russia, and was transferred to

Siberia Siberia ( ; , ) is an extensive geographical region comprising all of North Asia, from the Ural Mountains in the west to the Pacific Ocean in the east. It has formed a part of the sovereign territory of Russia and its predecessor states ...

, 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

. Wilchek has published over 400 scientific papers, and consulted various

biotech Biotechnology is a multidisciplinary field that involves the integration of natural sciences and engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists in the field are kn ...

companies. He was also in the party list of Mafdal and Meimad for the

Knesset The Knesset ( , ) is the Unicameralism, unicameral legislature of Israel. The Knesset passes all laws, elects the President of Israel, president and Prime Minister of Israel, prime minister, approves the Cabinet of Israel, cabinet, and supe ...

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 chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

, affinity labeling, affinity therapy, and the

avidin Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians and deposited in the whites of their eggs. Dimeric members of the avidin family are also found in some bacteria. In chicken egg white, a ...

biotin Biotin (also known as vitamin B7 or vitamin H) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. ...

system. The avidin-biotin complex is the highest

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

interaction in nature, and its utilization to

biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

integrates all of the former approaches. Other contributions include conversion of

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...

s to

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

s, and was the first to prove experimentally the equation of Forster on dependence of energy transfer on distance, an approach known today as

FRET A fret is any of the thin strips of material, usually metal wire, inserted laterally at specific positions along the neck or fretboard of a stringed instrument. Frets usually extend across the full width of the neck. On some historical inst ...

. He also studied the fine structure of these chromophores using

circular dichroism Circular dichroism (CD) is dichroism involving circular polarization, circularly polarized light, i.e., the differential Absorption (electromagnetic radiation), absorption of left- and right-handed light. Left-hand circular (LHC) and right-hand ci ...

. More recently, he participated in a research team who studied how

garlic Garlic (''Allium sativum'') is a species of bulbous flowering plants in the genus '' Allium''. Its close relatives include the onion, shallot, leek, chives, Welsh onion, and Chinese onion. Garlic is native to central and south Asia, str ...

works at the molecular level, thanks to a unique biotechnological procedure for producing large quantities of pure

allicin Allicin is an organosulfur compound obtained from garlic and leeks. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma of fresh garlic. Allicin is unstable and quickl ...

, garlic's main biologically active component.

Affinity chromatography

Affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

is a method of separating

biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...

mixtures, based on a highly specific biologic interaction such as that between

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

and

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

and substrate, or

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

and

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

. 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-tag A polyhistidine-tag, best known by the trademarked name His-tag, is an amino acid motif in proteins that typically consists of at least six histidine (''His'') residues, often at the N- or C-terminus of the protein. It is also known as a hexa hi ...

s or GST (glutathione-S-transferase) tags, which can be recognized by a metal ion ligand, such as

imidazole Imidazole (ImH) is an organic compound with the formula . It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. It can be classified as a heterocycle, specifically as a diazole. Many natural products, ...

. In 1971, Wilchek and colleagues applied this method to show that

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...

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

Affinity labeling

Affinity label is a

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

that is similar in structure to a particular substrate for a specific

. It is considered to be a class of irreversible inhibitors. These molecules covalently modify

active site In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate, the ''binding s ...

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 In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

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 An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of c ...

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 Sela, 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 Dextran is a complex branched glucan (polysaccharide derived from the condensation of glucose), originally derived from wine. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 ...

for drug delivery and targeting. This approach was later adopted by others and eventually led to efficient treatment of human

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

by recombinant humanized anti-HER2 antibody (

Herceptin Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together w ...

) in a mixture with

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

and doxorubicin. In 2003, Wilchek collaborated in a team who introduced a system based on antibody-directed enzyme prodrug therapy (

ADEPT An adept is an individual identified as having attained a specific level of knowledge, skill, or aptitude in doctrines relevant to a particular occult discipline, such as alchemy or magic. According to magical tradition, adepts stand out from ...

), using antibody-conjugated alliinase to produce a

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

agent, allicin, in situ (at the site) of the cancer

The avidin-biotin system

The

–

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 The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...

, 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.

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 Medicine, jointly with Pedro Cuatrecasas, "for the invention and development of

and its applications to biomedical sciences." * 1987: Pierce Prize for Biorecognition Technology * 1988: Elected Member of the Israel Academy of Sciences and Humanities * 1989: Doctor of Science, ''honoris causa'', University of Waterloo, Canada * 1989: Barnett Lecturer, Northeastern University, Boston * 1990:

Israel Prize The Israel Prize (; ''pras israél'') is an award bestowed by the State of Israel, and regarded as the state's highest cultural honor. History Prior to the Israel Prize, the most significant award in the arts was the Dizengoff Prize and in Israel ...

, in life sciences * 1990: Sarstedt Prize (Numbrecht, Germany) * 1993: Foreign Associate Member,

Institute of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...

, National Academy of Science, USA * 1995: Doctor of Science, ''honoris causa'', Bar Ilan University, Israel * 1996: International Distinguished Clinical Chemist Award, International Federation of Clinical Chemistry (IFCC) * 2000: Doctor of Science, ''honoris causa'', University Jyvaskyla, Finland * 2000: Honorary Doctorate, Ben-Gurion University of the Negev * 2002: Honorary Citizen, City of

Rehovot Rehovot (, / ) is a city in the Central District (Israel), Central District of Israel, about south of Tel Aviv. In it had a population of . Etymology Israel Belkind, founder of the Bilu (movement), Bilu movement, proposed the name "Rehovot ...

, Israel * 2004:

Wilhelm Exner Medal The Wilhelm Exner Medal has been awarded by the Austrian Industry Association, (ÖGV), for excellence in research and science since 1921. The medal is dedicated to Wilhelm Exner (1840–1931), former president of the Association, who initialize ...

.Editor, ÖGV. (2015). Wilhelm Exner Medal. Austrian Trade Association. ÖGV. Austria. * 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

References

External links

2 Researchers Share Prize in Medicine

The Wolf Prize in Medicine in 1987 (detail)
{{DEFAULTSORT:Wilchek, Meir 1935 births Israel Prize in life sciences recipients Israel Prize in life sciences recipients who were biochemists Members of the Israel Academy of Sciences and Humanities Wolf Prize in Medicine laureates 20th-century Polish Jews Polish emigrants to Israel Living people Academic staff of Weizmann Institute of Science Members of the European Academy of Sciences and Arts Members of the National Academy of Medicine