Myron L. Bender

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Myron Lee Bender
Born1924
St. Louis, Missouri
Died1988(1988-00-00) (aged 63–64)
Education Purdue University (B.S., Ph.D.)
Known for Hass–Bender oxidation
SpouseMuriel S. Bender
AwardsFellow of Merton College, Oxford University, National Academy of Sciences, 1968. Midwest Award of the American Chemical Society, 1972.
Scientific career
FieldsReaction mechanisms, biochemistry of enzyme action.
InstitutionsHarvard University, University of Chicago, Illinois Institute of Technology, Northwestern University
Doctoral advisor Henry B. Hass
Other academic advisors Paul D. Barlett, Frank H. Westheimer

Myron Lee Bender (1924–1988) was born in St. Louis, Missouri. He obtained his B.S. (1944) and his Ph.D. (1948) from Purdue University. The latter was under the direction of Henry B. Hass. After postdoctoral research under Paul D. Barlett (Harvard University), and Frank H. Westheimer (University of Chicago), he spent one year as a faculty member at the University of Connecticut. Thereafter, he was a professor of Chemistry at Illinois Institute of Technology in 1951, and then at Northwestern University in 1960. He worked primarily in the study of reaction mechanisms and the biochemistry of enzyme action. Myron L. Bender demonstrated the two-step mechanism of catalysis for serine proteases, nucleophilic catalysis in ester hydrolysis and intramolecular catalysis in water. He also showed that cyclodextrin can be used to investigate catalysis of organic reactions within the scope of host–guest chemistry. Finally, he and others reported on the synthesis of an organic compound as a model of an acylchymotrypsin intermediate.

Contents

During his career, Myron L. Bender was an active member of the Chicago Section of the American Chemical Society. He was elected a Fellow of Merton College, Oxford University, and to the National Academy of Sciences, the latter in 1968. He received an honorary degree from Purdue University in 1969. He was the recipient of the Midwest Award of the American Chemical Society in 1972.

Professor Bender retired from Northwestern in 1988. Both he and his wife, Muriel S. Bender, died that year.

Research

Research papers

Bender's initial work concerned mechanisms of chemical reactions, [1] and although this continued through his career he became increasingly interested in enzyme mechanisms, [2] especially that of α-chymotrypsin. [3] [4] [5] Later he broadened his interest to encompass other enzymes, such as acetylcholinesterase [6] and carboxypeptidase, [7] and others. [8]

Bender pioneered the use of p-nitrophenyl acetate as a model substrate for studying proteolysis, as it is particularly convenient in spectroscopic experiments. [9] [10] He likewise used imidazole as a model catalyst for shedding light on enzyme action. [11]

He also studied artificial enzymes, starting with modified subtilisin in which a serine residue was replaced by cysteine (replacing an ester group with a thiol). [12] Polgar and Bender laid stress on the fact that the modified enzyme was catalytically active, whereas Koshland and Neet, [13] who made essentially the same observation the same year, drew the opposite conclusion, that despite replacing group with one in principle more reactive, the modified enzyme was less effective as a catalyst than the unmodified enzyme. Philipp and Bender later did a detailed study of the catalytic differences between native subtilisin and thiolsubtilisin. [14] Bender also studied other artificial enzymes, [15] such as cycloamyloses, that were not simply modified natural enzymes.

Bender may have been the first to recognize that the specificity constant (, the ratio of catalytic constant to Michaelis constant) provides the best measure of enzyme specificity, [16] and to use the term specificity constant for it, as later recommended by the IUBMB. [17] Philipp and Bender proposed that this specificity constant is the same as the second-order rate constant for enzyme-substrate binding [18] for the most active substrates.

Reviews

Bender authored or co-authored several reviews, for example summarizing several years' work on α-chymotrypsin, [19] and proteolytic enzymes in general. [20]

Books

Bender's books primarily concerned catalysis, [21] especially catalysis by enzymes [22] and its underlying chemistry, [23] and also cyclodextrin chemistry; [24]

Bender Distinguished Summer Lecturers

The series of Myron L. Bender & Muriel S. Bender Distinguished Summer Lectures in Organic Chemistry was established in 1989 and hosted by the Department of Chemistry at Northwestern University. The scientists who have given these lectures include Julius Rebek (1990), JoAnne Stubbe (1992), Peter B. Dervan (1993), Marye Anne Fox (1994), Richard Lerner (1995), Eric Jacobsen (1997), Larry E. Overman (1998), Ronald Breslow (1999), Jean Fréchet (2000), Dale Boger (2001), |Barbara Imperiali (2003), François Diederich (2004), Christopher T. Walsh (2008), Stephen L. Buchwald (2009), Paul Wender (2010), and Kendall Houk (2011).

See also

Related Research Articles

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Catalysis is the increase in rate of a chemical reaction due to an added substance known as a catalyst. Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quickly, very small amounts of catalyst often suffice; mixing, surface area, and temperature are important factors in reaction rate. Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process of regenerating the catalyst.

<span class="mw-page-title-main">Chymotrypsin</span> Digestive enzyme

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<span class="mw-page-title-main">Enzyme</span> Large biological molecule that acts as a catalyst

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In chemistry, homogeneous catalysis is catalysis where the catalyst is in same phase as reactants, principally by a soluble catalyst a in solution. In contrast, heterogeneous catalysis describes processes where the catalysts and substrate are in distinct phases, typically solid-gas, respectively. The term is used almost exclusively to describe solutions and implies catalysis by organometallic compounds. Homogeneous catalysis is an established technology that continues to evolve. An illustrative major application is the production of acetic acid. Enzymes are examples of homogeneous catalysts.

<span class="mw-page-title-main">Acid catalysis</span> Chemical reaction

In acid catalysis and base catalysis, a chemical reaction is catalyzed by an acid or a base. By Brønsted–Lowry acid–base theory, the acid is the proton (hydrogen ion, H+) donor and the base is the proton acceptor. Typical reactions catalyzed by proton transfer are esterifications and aldol reactions. In these reactions, the conjugate acid of the carbonyl group is a better electrophile than the neutral carbonyl group itself. Depending on the chemical species that act as the acid or base, catalytic mechanisms can be classified as either specific catalysis and general catalysis. Many enzymes operate by general catalysis.

<span class="mw-page-title-main">Catalytic triad</span> Set of three coordinated amino acids

A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes. An acid-base-nucleophile triad is a common motif for generating a nucleophilic residue for covalent catalysis. The residues form a charge-relay network to polarise and activate the nucleophile, which attacks the substrate, forming a covalent intermediate which is then hydrolysed to release the product and regenerate free enzyme. The nucleophile is most commonly a serine or cysteine amino acid, but occasionally threonine or even selenocysteine. The 3D structure of the enzyme brings together the triad residues in a precise orientation, even though they may be far apart in the sequence.

<span class="mw-page-title-main">Enzyme kinetics</span> Study of biochemical reaction rates catalysed by an enzyme

Enzyme kinetics is the study of the rates of enzyme-catalysed chemical reactions. In enzyme kinetics, the reaction rate is measured and the effects of varying the conditions of the reaction are investigated. Studying an enzyme's kinetics in this way can reveal the catalytic mechanism of this enzyme, its role in metabolism, how its activity is controlled, and how a drug or a modifier might affect the rate.

<span class="mw-page-title-main">Frank Westheimer</span> American chemist

Frank Henry Westheimer NAS ForMemRS APS was an American chemist. He taught at the University of Chicago from 1936 to 1954, and at Harvard University from 1953 to 1983, becoming the Morris Loeb Professor of Chemistry in 1960, and Professor Emeritus in 1983. The Westheimer medal was established in his honor in 2002.

The alpha effect refers to the increased nucleophilicity of an atom due to the presence of an adjacent (alpha) atom with lone pair electrons. This first atom does not necessarily exhibit increased basicity compared with a similar atom without an adjacent electron-donating atom, resulting in a deviation from the classical Brønsted-type reactivity-basicity relationship. In other words, the alpha effect refers to nucleophiles presenting higher nucleophilicity than the predicted value obtained from the Brønsted basicity. The representative examples would be high nucleophilicities of hydroperoxide (HO2) and hydrazine (N2H4). The effect is now well established with numerous examples and became an important concept in mechanistic chemistry and biochemistry. However, the origin of the effect is still controversial without a clear winner.

<span class="mw-page-title-main">Enzyme catalysis</span> Catalysis of chemical reactions by specialized proteins known as enzymes

Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs at a localized site, called the active site.

<span class="mw-page-title-main">W. Wallace Cleland</span>

William Wallace Cleland (January 6, 1930 – March 6, 2013, often cited as W. W. Cleland, and known almost universally as "Mo Cleland", was a University of Wisconsin-Madison biochemistry professor. His research was concerned with enzyme reaction mechanism and enzyme kinetics, especially multiple-substrate enzymes. He was elected to the National Academy of Sciences in 1985.

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<span class="mw-page-title-main">Borinic acid</span> Chemical compound

Borinic acid, also known as boronous acid, is an oxyacid of boron with formula H
2
BOH
. Borinate is the associated anion of borinic acid with formula H
2
BO
; however, being a Lewis acid, the form in basic solution is H
2
B(OH)
2
.

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References

  1. Bender, Myron L. (1951). "Oxygen Exchange as Evidence for the Existence of an Intermediate in Ester Hydrolysis". Journal of the American Chemical Society. 73 (4): 1626–1629. doi:10.1021/ja01148a063.
  2. Bender, Myron L.; Turnquest, Byron W. (1957). "General Basic Catalysis of Ester Hydrolysis and Its Relationship to Enzymatic Hydrolysis1". Journal of the American Chemical Society. 79 (7): 1656–1662. doi:10.1021/ja01564a035.
  3. Bender, Myron L.; Kemp, Kenneth C. (1957). "The Kinetics of the α-Chymotrypsin-catalyzed Oxygen Exchange of Carboxylic Acids1". Journal of the American Chemical Society. 79: 116–120. doi:10.1021/ja01558a030.
  4. Bender, Myron L.; Glasson, William A. (1960). "The Kinetics of the α-Chymotrypsin-catalyzed Hydrolysis and Methanolysis of Acetyl-L-phenylalanine Methyl Ester. Evidence for the Specific Binding of Water on the Enzyme Surface1". Journal of the American Chemical Society. 82 (13): 3336–3342. doi:10.1021/ja01498a027.
  5. Bender, Myron L.; Zerner, Burt (1961). "The formation of the acyl-enzyme intermediate, trans-cinnamoyl-α-chymotrypsin, in the hydrolyses of non-labile trans-cinnamic acid esters1". Journal of the American Chemical Society. 83 (10): 2391–2392. doi:10.1021/ja01471a040.
  6. Bender, Myron L.; Stoops, James K. (1965). "Titration of the Active Sites of Acetylcholinesterase". Journal of the American Chemical Society. 87 (7): 1622–1623. doi:10.1021/ja01085a045. PMID   14302679.
  7. Bender, M. L.; Whitaker, J. R.; Menger, F. (1965). "The Effect of Enzyme Acetylation on the Kinetics of the Carboxypeptidase-A-Catalyzed Hydrolysis of Hippuryl-L-Phenyllactic Acid". Proceedings of the National Academy of Sciences. 53 (4): 711–716. doi: 10.1073/pnas.53.4.711 . PMC   221055 . PMID   14324526.
  8. Bender, Myron L.; Begué-Cantón, Maria Luisa Begué; Blakeley, Robert L.; Brubacher, Lewis J.; Feder, Joseph; Gunter, Claude R.; Kézdy, Ferenc J.; Killheffer, John V.; Marshall, Thomas H.; Miller, Charles G.; Roeske, Roger W.; Stoops, James K. (1966). "The Determination of the Concentration of Hydrolytic Enzyme Solutions: α-Chymotrypsin, Trypsin, Papain, Elastase, Subtilisin, and Acetylcholinesterase". Journal of the American Chemical Society. 88 (24): 5890–5913. doi:10.1021/ja00976a034. PMID   5980876.
  9. Bender, Myron L.; Turnquest, Byron W. (1957). "The Imidazole-catalyzed Hydrolysis of p-Nitrophenyl Acetate1". Journal of the American Chemical Society. 79 (7): 1652–1655. doi:10.1021/ja01564a034.
  10. Kezdy, Ferenc J.; Bender, Myron L. (1962). "The Kinetics of the α-Chymotrypsin-Catalyzed Hydrolysis of p-Nitrophenyl Acetate". Biochemistry. 1 (6): 1097–1106. doi:10.1021/bi00912a021. PMID   14032227.
  11. Westheimer, F. H.; Bender, Myron L. (1962). "Imidazole Catalysis of the Hydrolysis of δ-Thiovalerolactone". Journal of the American Chemical Society. 84 (24): 4908–4909. doi:10.1021/ja00883a055.
  12. Polgar, Laszlo; Bender, Myron L. (1966). "A New Enzyme Containing a Synthetically Formed Active Site. Thiol-Subtilisin1". Journal of the American Chemical Society. 88 (13): 3153–3154. doi:10.1021/ja00965a060.
  13. Neet, K. E.; Koshland, D. E. (1966). "The conversion of serine at the active site of subtilisin to cysteine: A "chemical mutation"". Proceedings of the National Academy of Sciences. 56 (5): 1606–1611. Bibcode:1966PNAS...56.1606N. doi: 10.1073/pnas.56.5.1606 . PMC   220044 . PMID   5230319.
  14. Philipp, Manfred; Bender, M. L. (1983). "Kinetics of subtilisin and thiolsubtilisin". Molecular and Cellular Biochemistry. 51 (1): 5–32. doi:10.1007/BF00215583. PMID   6343835. S2CID   24136200.
  15. Vander Jagt, David L.; Killian, Frederick L.; Bender, M. L. (1970). "Cycloamyloses as enzyme models. Effects of inclusion complex formation on intramolecular participation". Journal of the American Chemical Society. 92 (4): 1016–1022. doi:10.1021/ja00707a046. PMID   5451006.
  16. Brot, Frederick E.; Bender, Myron L. (1969). "Use of the specificity constant of α-chymotrypsin". Journal of the American Chemical Society. 91 (25): 7187–7191. doi:10.1021/ja01053a050.
  17. Cornish-Bowden, A. (2014). "Current IUBMB recommendations on enzyme nomenclature and kinetics". Perspectives in Science. 1 (1–6): 74–87. Bibcode:2014PerSc...1...74C. doi: 10.1016/j.pisc.2014.02.006 .
  18. Philipp, Manfred; Bender, Myron L. (1973). "Is binding the rate-limiting step in acylation of alpha-chymotrypsin by specific substrates?". Nature New Biology. 241 (106): 44. doi: 10.1038/newbio241044a0 . PMID   4512333.
  19. Bender, Myron L.; Kezdy, Ferenc J. (1964). "The Current Status of the α-Chymotrypsin Mechanism". Journal of the American Chemical Society. 86 (18): 3704–3714. doi:10.1021/ja01072a020.
  20. Bender, M. L.; Kezdy, F. J. (1965). "Mechanism of Action of Proteolytic Enzymes". Annual Review of Biochemistry. 34: 49–76. doi:10.1146/annurev.bi.34.070165.000405. PMID   14321178.
  21. Bender, Myron L. (1971). Mechanisms of Homogeneous Catalysis from Protons to Proteins. Wiley-Interscience. ISBN   978-0471065005.
  22. Bender, M. L.; Brubacher, Lewis J. (1973). Catalysis and Enzyme Action. McGraw-Hill. ISBN   978-0070044500.
  23. Bender, Myron L.; Bender, Mike; Bergeron, Raymond J.; Komiyama, Makoto (1984). The Bioorganic Chemistry of Enzymatic Catalysis. Wiley. ISBN   978-0471059912.
  24. Bender, Myron L; Kobiyama, M. (1978). Cyclodextrin Chemistry. Berlin: Springer-Verlag. ISBN   978-3540085775.