Meir Wilchek (Hebrew: מאיר אשר וילצ'ק, born 17 October 1935) is an Israeli biochemist. He is a professor at the

Weizmann Institute of Science The Weizmann Institute of Science ( he, מכון ויצמן למדע ''Machon Vaitzman LeMada'') is a public research university in Rehovot, Israel, established in 1934, 14 years before the State of Israel. It differs from other Israeli unive ...

Early life and education

Meir Wilchek was born in

Warsaw Warsaw ( pl, Warszawa, ), officially the Capital City of Warsaw,, abbreviation: ''m.st. Warszawa'' is the capital and largest city of Poland. The metropolis stands on the River Vistula in east-central Poland, and its population is officia ...

, Poland, scion of a rabbinical family. During the

Holocaust The Holocaust, also known as the Shoah, was the genocide of European Jews during World War II. Between 1941 and 1945, Nazi Germany and its collaborators systematically murdered some six million Jews across German-occupied Europe; ...

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

Siberia Siberia ( ; rus, Сибирь, r=Sibir', p=sʲɪˈbʲirʲ, a=Ru-Сибирь.ogg) is an extensive region, geographical region, constituting all of North Asia, from the Ural Mountains in the west to the Pacific Ocean in the east. It has been a ...

, while his father, who served as a community rabbi in Warsaw, was killed in

Flossenbürg concentration camp Flossenbürg was a Nazi concentration camp built in May 1938 by the SS Main Economic and Administrative Office. Unlike other concentration camps, it was located in a remote area, in the Fichtel Mountains of Bavaria, adjacent to the town of Flo ...

. He survived, and immigrated to Israel in 1949 with his mother and sister. He graduated with B.Sc. in chemistry from

Bar Ilan Bar-Ilan University (BIU, he, אוניברסיטת בר-אילן, ''Universitat Bar-Ilan'') is a public research university in the Tel Aviv District city of Ramat Gan, Israel. Established in 1955, Bar Ilan is Israel's second-largest academic i ...

university and Ph.D. in biochemistry from the

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

biotech Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...

companies. He was also in the party list of

Mafdal The National Religious Party ( he, מִפְלָגָה דָּתִית לְאֻומִּית, ''Miflaga Datit Leumit'', commonly known in Israel by its Hebrew acronym Mafdal, ) was a political party in Israel representing the religious Zionist movem ...

and

Meimad Meimad ( he, מימד, an acronym for ''Medina Yehudit, Medina Demokratit'' (), lit., ''Jewish State, Democratic State'') is a moderate to left-wing religious Zionist political party in Israel. Founded in 1999, it is based on the ideology of the ...

for the

Knesset The Knesset ( he, הַכְּנֶסֶת ; "gathering" or "assembly") is the unicameral legislature of Israel. As the supreme state body, the Knesset is sovereign and thus has complete control of the entirety of the Israeli government (with ...

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 label Affinity labels are a class of enzyme inhibitors that covalently bind to their target causing its inactivation. The hallmark of an affinity label is the use of a targeting moiety to specifically and reversibly deliver a weakly reactive group to the ...

ing, affinity therapy, and the avidin- biotin 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 Par ...

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 and ...

integrates all of the former approaches. Other contributions include conversion of serines to cysteines, and was the first to prove experimentally the equation of Forster on dependence of energy transfer on distance, 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 Allicin is an organosulfur compound obtained from garlic, a species in the family Alliaceae. It was first isolated and studied in the laboratory by Chester J. Cavallito and John Hays Bailey in 1944. When fresh garlic is chopped or crushed, th ...

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

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

and

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

and substrate, or

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

and

ligand In coordination chemistry, a ligand is an ion or molecule ( 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 elec ...

. 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 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 hexa histidine-tag, 6xHis-tag, His6 tag, by the US tra ...

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 C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-a ...

. 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 fu ...

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 or hæmoperfusion (see spelling differences) is a method of filtering the blood extracorporeally (that is, outside the body) to remove a toxin. As with other extracorporeal methods, such as hemodialysis (HD), hemofiltration (HF), ...

Affinity labeling

Affinity label Affinity labels are a class of enzyme inhibitors that covalently bind to their target causing its inactivation. The hallmark of an affinity label is the use of a targeting moiety to specifically and reversibly deliver a weakly reactive group to the ...

is a

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

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 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 ...

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 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 Michael Sela ( he, מיכאל סלע; Mieczysław Salomonowicz; 2 March 1924 – 27 May 2022) was an Israeli immunologist of Polish Jewish origin. He was the W. Garfield Weston Professor of Immunology at the Weizmann Institute of Science in Re ...

, Ester Hurwitz, and

Ruth Arnon Ruth Arnon (Hebrew: רות ארנון �ut aʁ'non born in Tel Aviv on June 1, 1933) is an Israeli biochemist and codeveloper of the multiple sclerosis drug Copaxone. She is currently the Paul Ehrlich Professor of Immunology at the Weizmann Ins ...

. 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 cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

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 wi ...

) in a mixture with

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical canc ...

and

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

. 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 author or organization. He or she stands out from others with their great abilities. All human quali ...

), using antibody-conjugated

alliinase In enzymology, an alliin lyase () is an enzyme that catalyzes the chemical reaction :an ''S''-alkyl-L-cysteine ''S''-oxide \rightleftharpoons an alkyl sulfenate + 2-aminoacrylate Hence, this enzyme has one substrate, ''S''-alkyl-L-cysteine ...

to produce a cytotoxic agent, allicin, in situ (at the site) of the cancer

The avidin-biotin system

The avidin– 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 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 uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...

ELISPOT The enzyme-linked immune absorbent spot (ELISpot) is a type of assay that focuses on quantitatively measuring the frequency of cytokine secretion for a single cell. The ELISpot Assay is also a form of immunostaining since it is classified as a tec ...

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 The Wolf Prize in Medicine is awarded annually 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 ...

, jointly with

Pedro Cuatrecasas Pedro Cuatrecasas (born 27 September 1936) is an American biochemist and an Adjunct Professor of Pharmacology & Medicine at the University of California San Diego. Birth and education Pedro Cuatrecasas was born in 1936 in Madrid, Spain. He com ...

, "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 Israel Academy of Sciences and Humanities, based in Jerusalem, was established in 1961 by the State of Israel to foster contact between Israeli scholars in the sciences and humanities and create a think tank for advising the government on re ...

* 1989 Doctor of Science, ''honoris causa'', University of Waterloo, Canada * 1989 Barnett Lecturer, Northeastern University, Boston * 1990 Israel Prize, in life sciences * 1990 Sarstedt Prize (Numbrecht, Germany) * 1993 Foreign Associate Member, Institute of Medicine, 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, 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 The EMET Prize for Art, Science and Culture is an Israeli prize awarded annually for excellence in academic and professional achievements that have far-reaching influence and make a significant contribution to society. Prizes are awarded in the fol ...

, 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 Weizmann Institute of Science faculty Members of the European Academy of Sciences and Arts Members of the National Academy of Medicine