Meir Wilchek
Born (1935-10-17) 17 October 1935
Warsaw, Poland
NationalityIsraeli
Alma materBar Ilan University and the Weizmann Institute of Science
Known forAffinity chromatography
AwardsWolf Prize, Israel Prize
Scientific career
FieldsBiochemist
InstitutionsWeizmann Institute of Science

Meir Wilchek (Hebrew: מאיר אשר וילצ'ק, born 17 October 1935) is an Israeli biochemist.[1] He is a professor at the Weizmann Institute of Science.

Early life and education

Meir Wilchek was born in Warsaw, 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.

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 labeling, 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 serines to cysteines,[2] and was the first to prove experimentally the equation of Forster on dependence of energy transfer on distance,[3] an approach known today as FRET. He also studied the fine structure of these chromophores using circular dichroism.[4] 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.[5]

Affinity chromatography

Affinity chromatography[6] 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.[7] 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[8]

Affinity labeling

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 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[9]).

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 Sela, Ester Hurwitz, and Ruth Arnon. In 1975, they applied drug-conjugated antibodies for the targeted delivery of cytotoxic compounds to cancer cells.[10] 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[11]

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, ELISA, ELISPOT and pull-down assays.[12] 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,[13] which aids in the design of specific artificial recognition sites.[14]

Honors and awards

See also

References

  1. ↑ who, M.W. (1990). Who's Who in the World: 1991-1992. Marquis Who's Who. ISBN 9780837911106. Retrieved 2014-12-13.
  2. ↑ Zioudrou, C., Wilchek, M., and Patchornik, A. (1965). "Conversion of the L-serine residue to an L-cysteine residue in peptides". Biochemistry. 4 (9): 1811–1822. doi:10.1021/bi00885a018.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ↑ Edelhoch, H., Brand, L., Wilchek, M. (1967). "Fluorescence studies with tryptophyl peptides". Biochemistry. 6 (2): 547–559. doi:10.1021/bi00854a024. PMID 6047638.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ↑ Edelhoch, H., Lippoldt, R.E., Wilchek, M. (1968). "The circular dichroism of tyrosyl and tryptophanyl diketopiperazines". J. Biol. Chem. 243 (18): 4799–4805. doi:10.1016/S0021-9258(18)93189-3. PMID 5687722.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ "Therapeutic Effects of Garlic Clarified by Weizmann Institute Research". Weizmann Institute of Science. 14 October 1997. Archived from the original on 8 November 2005.
  6. ↑ Cuatrecasas P, Wilchek M, Anfinsen CB (1968). "Selective enzyme purification by affinity chromatography". Proc. Natl. Acad. Sci. USA. 61 (2): 636–43. Bibcode:1968PNAS...61..636C. doi:10.1073/pnas.61.2.636. PMC 225207. PMID 4971842.
  7. ↑ Wilchek, M., Salomon, Y., Lowe, M., and Selinger, Z. (1971). "Conversion of protein kinase to a cyclic AMP independent form by affinity chromatography on N0-caproyl 3′,5′-cyclic adenosine monophosphate-Sepharose". Biochem. Biophys. Res. Commun. 45 (5): 1177–1184. doi:10.1016/0006-291X(71)90142-2. PMID 4332593.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Wilchek, M. (1972). "Purification of the heme peptide of cytochrome c by affinity chromatography". Anal. Biochem. 49 (2): 572–575. doi:10.1016/0003-2697(72)90464-2. PMID 4343271.
  9. ↑ Strausbauch, P.H., Weinstein, Y., Wilchek, M., Shaltiel, S., Givol, D. (1971). "A homologous series of affinity labeling reagents and their use in the study of antibody binding sites". Biochemistry. 10 (13): 2631–2638. doi:10.1021/bi00799a029. PMID 5105033.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ↑ Hurwitz, E., Levy, R., Maron, R., Wilchek, M., Arnon, R., and Sela, M. (1975). "The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities". Cancer Res. 35 (5): 1175–1181. PMID 164279.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ↑ Miron, T., Mironchik, M., Mirelman, D., Wilchek, M., and Rabinkov, A. (2003). "Inhibition of tumor growth by a novel approach: In situ allicin generation using targeted alliinase delivery". Mol. Cancer Ther. 2 (12): 1295–1301. PMID 14707270.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ↑ Wilchek, M. & Bayer, E.A. (1988). "The avidin-biotin complex in bioanalytical applications". Anal. Biochem. 171 (1): 1–32. doi:10.1016/0003-2697(88)90120-0. PMID 3044183.
  13. ↑ Livnah, O., Bayer, E.A., Wilchek, M., and Sussman, J. (1993). "Three-dimensional structures of avidin and the avidin-biotin complex". Proc. Natl. Acad. Sci. 90 (11): 5076–5080. Bibcode:1993PNAS...90.5076L. doi:10.1073/pnas.90.11.5076. PMC 46657. PMID 8506353.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ↑ Domovich-Eisenberg, Y., Pazy, Y., Nir, O., Raboy, B., Bayer, E.A., Wilchek, M., and Livnah, O. (2004). "Structural elements responsible for conversion of streptavidin to a pseudoenzyme". Proc. Natl. Acad. Sci. 101 (16): 5916–5921. Bibcode:2004PNAS..101.5916E. doi:10.1073/pnas.0308541101. PMC 395898. PMID 15079055.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ↑ The Wolf Prize in Medicine Archived February 26, 2009, at the Wayback Machine
  16. ↑ "Israel Prize Official Site - Recipients in 1990 (in Hebrew)".
  17. ↑ Editor, ÖGV. (2015). Wilhelm Exner Medal. Austrian Trade Association. ÖGV. Austria.
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