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Meir Wilchek

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Meir Wilchek
Born(1935-10-17)17 October 1935(age 88)
Warsaw,Poland
NationalityIsraeli
Alma materBar Ilan Universityand theWeizmann 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 theWeizmann Institute of Science.

Early life and education[edit]

Meir Wilchek was born inWarsaw,Poland, scion of a rabbinical family. During theHolocaust,he escaped from the German-occupied territories to the territories occupied by Russia, and was transferred toSiberia,while his father, who served as a community rabbi in Warsaw, was killed inFlossenbürg concentration camp.He survived, and immigrated to Israel in 1949 with his mother and sister. He graduated with B.Sc. in chemistry fromBar Ilanuniversity and Ph.D. in biochemistry from theWeizmann Institute of Science.Wilchek has published over 400 scientific papers, and consulted variousbiotechcompanies. He was also in the party list ofMafdalandMeimadfor theKnesset.

Scientific contributions[edit]

Meir Wilchek is known for his research in the field of biorecognition or affinity phenomenon, and its various application, e.g. foraffinity chromatography,affinity labeling,affinity therapy, and theavidin-biotinsystem. The avidin-biotin complex is the highestaffinityinteraction in nature, and its utilization tobiochemistryintegrates all of the former approaches.

Other contributions include conversion ofserinestocysteines,[2]and was the first to prove experimentally the equation of Forster on dependence of energy transfer on distance,[3]an approach known today asFRET.He also studied the fine structure of these chromophores usingcircular dichroism.[4]More recently, he participated in a research team who studied howgarlicworks at the molecular level, thanks to a unique biotechnological procedure for producing large quantities of pureallicin,garlic's main biologically active component.[5]

Affinity chromatography[edit]

Affinity chromatography[6]is a method of separatingbiochemicalmixtures, based on a highly specific biologic interaction such as that betweenantigenandantibody,enzymeandsubstrate,orreceptorandligand.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. usingHis-tagsor GST (glutathione-S-transferase) tags, which can be recognized by a metal ion ligand, such asimidazole.

In 1971, Wilchek and colleagues applied this method to show thatprotein kinaseis 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 modernhemoperfusion[8]

Affinity labeling[edit]

Affinity labelis amoleculethat is similar in structure to a particularsubstratefor a specificenzyme.It is considered to be a class ofirreversible inhibitors.These molecules covalently modifyactive siteresidues in order to elucidate the structure of the active site. Using this method, Wilchek collaborated with a team who proved that thebinding siteofantibodieslies in the Fv portion of the molecule and involves three hypervariable sites, today called thecomplementarity-determining regions(CDRs[9]).

Affinity therapy[edit]

Affinity therapy, orimmunotoxinsis 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 withMichael Sela,Ester Hurwitz, andRuth 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 asdextranfor drug delivery and targeting. This approach was later adopted by others and eventually led to efficient treatment of humanbreast cancerby recombinant humanized anti-HER2 antibody (Herceptin) in a mixture withpaclitaxelanddoxorubicin.In 2003, Wilchek collaborated in a team who introduced a system based on antibody-directed enzyme prodrug therapy (ADEPT), using antibody-conjugatedalliinaseto produce acytotoxicagent, allicin, in situ (at the site) of the cancer[11]

The avidin-biotin system[edit]

Theavidin–biotinsystem 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 thebiotinylatedbinder 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 tobiotinylateantibodies and other biomolecules. Today, the system is applied in research and diagnostics as well as medical devices and pharmaceuticals. Examples includewestern blot,ELISA,ELISPOTand 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 the3D structureof the avidin–biotin complex by X-ray crystallography,[13]which aids in the design of specific artificial recognition sites.[14]

Honors and awards[edit]

See also[edit]

References[edit]

  1. ^who, M.W. (1990).Who's Who in the World: 1991-1992.Marquis Who's Who.ISBN9780837911106.Retrieved2014-12-13.
  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.PMID6047638.{{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.PMID5687722.{{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 fromthe originalon 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.PMC225207.PMID4971842.
  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.PMID4332593.{{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.PMID4343271.
  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.PMID5105033.{{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.PMID164279.{{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.PMID14707270.{{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.PMID3044183.
  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.PMC46657.PMID8506353.{{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.PMC395898.PMID15079055.{{cite journal}}:CS1 maint: multiple names: authors list (link)
  15. ^The Wolf Prize in MedicineArchivedFebruary 26, 2009, at theWayback 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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