DOI: 10.1126/science.3787261. Catalytic Antibodies

Catalytic Antibodies

10.1126/science.3787261

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Monoclonal antibodies elicited to haptens that are analogs of the transition state for hydrolysis of carboxylic esters behaved as enzymic catalysts with the appropriate substrates. These substrates are distinguished by the structural congruence of both hydrolysis products with haptenic fragments. The haptens were potent inhibitors of this esterolytic activity, in agreement with their classification as transition state analogs. Mechanisms are proposed to account for the different chemical behavior of these antibodies with two types of ester substrates. The generation of an artificial enzyme through transition state stabilization by antibodies was thus demonstrated. These studies indicate a potentially general approach to catalyst design.

Bibliography

Tramontano, A., Janda, K. D., & Lerner, R. A. (1986). Catalytic Antibodies. Science, 234(4783), 1566â1570.

Authors 3

Alfonso Tramontano (first)
Kim D. Janda (additional)
Richard A. Lerner (additional)

References 30 Referenced 573

BARTLETT, P.A., PHOSPHONAMIDATES AS TRANSITION-STATE ANALOG INHIBITORS OF THERMOLYSIN, BIOCHEMISTRY 22: 4618 (1983). (10.1021/bi00289a002) / BIOCHEMISTRY (1983)
BENDER, M.L., BIOORGANIC CHEM ENZY: 150 (1984). / BIOORGANIC CHEM ENZY (1984)
CHABEREK, S, STABILITY OF METAL CHELATES .1. IMINODIACETIC AND IMINODIPROPIONIC ACIDS, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 74: 5052 (1952). (10.1021/ja01140a018) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1952)
CHRISTIANSON, D.W., STRUCTURE OF THE COMPLEX BETWEEN AN UNEXPECTEDLY HYDROLYZED PHOSPHONAMIDATE INHIBITOR AND CARBOXYPEPTIDASE-A, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 108: 545 (1986). (10.1021/ja00263a052) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1986)
FERSHT, A, ENZYME STRUCTURE MEC: 311 (1985). / ENZYME STRUCTURE MEC (1985)
GALARDY, R.E., INHIBITION OF ANGIOTENSIN CONVERTING ENZYME BY PHOSPHONIC AMIDES AND PHOSPHONIC-ACIDS, BIOCHEMISTRY 22: 1990 (1983). (10.1021/bi00277a039) / BIOCHEMISTRY (1983)
HANGAUER, D.G., AN INTERACTIVE COMPUTER-GRAPHICS STUDY OF THERMOLYSIN-CATALYZED PEPTIDE CLEAVAGE AND INHIBITION BY N-CARBOXYMETHYL DIPEPTIDES, BIOCHEMISTRY 23: 5730 (1984). (10.1021/bi00319a011) / BIOCHEMISTRY (1984)
IMPERIALI, B, INHIBITION OF SERINE PROTEASES BY PEPTIDYL FLUOROMETHYL KETONES, BIOCHEMISTRY 25: 3760 (1986). (10.1021/bi00361a005) / BIOCHEMISTRY (1986)
JACOBSEN, N.E., A PHOSPHONAMIDATE DIPEPTIDE ANALOG AS AN INHIBITOR OF CARBOXYPEPTIDASE-A, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 103: 654 (1981). (10.1021/ja00393a026) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1981)
JENCKS, W.P., BINDING-ENERGY, SPECIFICITY, AND ENZYMIC CATALYSIS - CIRCE EFFECT, ADVANCES IN ENZYMOLOGY AND RELATED AREAS OF MOLECULAR BIOLOGY 43: 219 (1975). / ADVANCES IN ENZYMOLOGY AND RELATED AREAS OF MOLECULAR BIOLOGY (1975)
JENCKS, W.P., CATALYSIS CHEM ENZYM: 288 (1969). / CATALYSIS CHEM ENZYM (1969)
JENCKS, W.P., CATALYSIS CHEM ENZYM: CH10 (1969). / CATALYSIS CHEM ENZYM (1969)
KOHEN, F, ANTIBODY-ENHANCED HYDROLYSIS OF STEROID ESTERS, BIOCHIMICA ET BIOPHYSICA ACTA 629: 328 (1980). (10.1016/0304-4165(80)90105-1) / BIOCHIMICA ET BIOPHYSICA ACTA (1980)
KOHEN, F, MONOCLONAL IMMUNOGLOBULIN-G AUGMENTS HYDROLYSIS OF AN ESTER OF THE HOMOLOGOUS HAPTEN - ESTERASE-LIKE ACTIVITY OF THE ANTIBODY-CONTAINING SITE, FEBS LETTERS 111: 427 (1980). (10.1016/0014-5793(80)80842-8) / FEBS LETTERS (1980)
LERNER, R.A., ANTIBODIES OF PREDETERMINED SPECIFICITY IN BIOLOGY AND MEDICINE, ADVANCES IN IMMUNOLOGY 36: 1 (1984). (10.1016/S0065-2776(08)60898-6) / ADVANCES IN IMMUNOLOGY (1984)
10.1126/science.180.4082.149
LISCOMB, W.N., ACC CHEM RES 15: 232 (1982). (10.1021/ar00080a001) / ACC CHEM RES (1982)
MONZINGO, A.F., BINDING OF N-CARBOXYMETHYL DIPEPTIDE INHIBITORS TO THERMOLYSIN DETERMINED BY X-RAY CRYSTALLOGRAPHY - A NOVEL CLASS OF TRANSITION-STATE ANALOGS FOR ZINC PEPTIDASES, BIOCHEMISTRY 23: 5724 (1984). (10.1021/bi00319a010) / BIOCHEMISTRY (1984)
PAULING, L, AM SCIENTIST 36: 51 (1948). / AM SCIENTIST (1948)
10.1126/science.3787262
RASO, V, ANTIBODY-ENZYME ANALOGY - COMPARISON OF ENZYMES AND ANTIBODIES SPECIFIC FOR PHOSPHOPYRIDOXYLTYROSINE, BIOCHEMISTRY 14: 591 (1975). (10.1021/bi00674a020) / BIOCHEMISTRY (1975)
RASO, V, ANTIBODY-ENZYME ANALOGY - CHARACTERIZATION OF ANTIBODIES TO PHOSPHOPYRIDOXYLTYROSINE DERIVATIVES, BIOCHEMISTRY 14: 584 (1975). (10.1021/bi00674a019) / BIOCHEMISTRY (1975)
REARDAN, D.T., ANTIBODIES AGAINST METAL-CHELATES, NATURE 316: 265 (1985). (10.1038/316265a0) / NATURE (1985)
THOMPSON, R.C., USE OF PEPTIDE ALDEHYDES TO GENERATE TRANSITION-STATE ANALOGS OF ELASTASE, BIOCHEMISTRY 12: 47 (1973). (10.1021/bi00725a009) / BIOCHEMISTRY (1973)
TRAMONTANO, A, CHEMICAL-REACTIVITY AT AN ANTIBODY-BINDING SITE ELICITED BY MECHANISTIC DESIGN OF A SYNTHETIC ANTIGEN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83: 6736 (1986). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1986)
WALSH, C, ENZYMATIC REACTION M: 43 (1979). / ENZYMATIC REACTION M (1979)
WEAVER, L.H., CRYSTALLOGRAPHIC STUDY OF COMPLEX OF PHOSPHORAMIDON WITH THERMOLYSIN - MODEL FOR PRESUMED CATALYTIC TRANSITION-STATE AND FOR BINDING OF EXTENDED SUBSTRATES, JOURNAL OF MOLECULAR BIOLOGY 114: 119 (1977). (10.1016/0022-2836(77)90286-8) / JOURNAL OF MOLECULAR BIOLOGY (1977)
WESTERIK, J.O., ALDEHYDES AS INHIBITORS OF PAPAIN, JOURNAL OF BIOLOGICAL CHEMISTRY 247: 8195 (1972). (10.1016/S0021-9258(20)81828-6) / JOURNAL OF BIOLOGICAL CHEMISTRY (1972)
WOLFENDEN, R, ANALOG APPROACHES TO STRUCTURE OF TRANSITION-STATE IN ENZYME REACTIONS, ACCOUNTS OF CHEMICAL RESEARCH 5: 10 (1972). (10.1021/ar50049a002) / ACCOUNTS OF CHEMICAL RESEARCH (1972)
WOLFENDEN R TRANSITION STATES 4 (1978).

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 4:28 p.m.)
Deposited	1 year, 7 months ago (Jan. 14, 2024, 5:17 a.m.)
Indexed	1 month, 1 week ago (July 25, 2025, 6:06 a.m.)
Issued	38 years, 8 months ago (Dec. 19, 1986)
Published	38 years, 8 months ago (Dec. 19, 1986)
Published Print	38 years, 8 months ago (Dec. 19, 1986)

Funders 0

None

BibTeX

@article{Tramontano_1986, title={Catalytic Antibodies}, volume={234}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.3787261}, DOI={10.1126/science.3787261}, number={4783}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Tramontano, Alfonso and Janda, Kim D. and Lerner, Richard A.}, year={1986}, month=dec, pages={1566–1570} }

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      [
        1986,
        12,
        19
      ]
    ]
  },
  "references-count": 30,
  "journal-issue": {
    "issue": "4783",
    "published-print": {
      "date-parts": [
        [
          1986,
          12,
          19
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.3787261"
  ],
  "URL": "http://dx.doi.org/10.1126/science.3787261",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1986,
        12,
        19
      ]
    ]
  }
}