Antibodies with infinite affinity

A. J. Chmura, M. S. Orton, C. F. Meares

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, we engineered complementary reactive groups in the antibody binding pocket and the ligand, so that they would be in close proximity in the antibody/ligand complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are very large, allowing a covalent reaction to link the two together. By eliminating the dissociation of the ligand from the antibody, we have made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs.

Original languageEnglish (US)
Pages (from-to)8480-8484
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number15
DOIs
StatePublished - Jul 17 2001

Fingerprint

Ligands
Antibodies
Immunologic Techniques
Antibody Specificity
Avidin
Cross Reactions
Biotin
Antibody Formation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Antibodies with infinite affinity. / Chmura, A. J.; Orton, M. S.; Meares, C. F.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 15, 17.07.2001, p. 8480-8484.

Research output: Contribution to journalArticle

Chmura, A. J. ; Orton, M. S. ; Meares, C. F. / Antibodies with infinite affinity. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 15. pp. 8480-8484.
@article{79da96444cee430c93394fa5bb9d66c8,
title = "Antibodies with infinite affinity",
abstract = "Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, we engineered complementary reactive groups in the antibody binding pocket and the ligand, so that they would be in close proximity in the antibody/ligand complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are very large, allowing a covalent reaction to link the two together. By eliminating the dissociation of the ligand from the antibody, we have made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs.",
author = "Chmura, {A. J.} and Orton, {M. S.} and Meares, {C. F.}",
year = "2001",
month = "7",
day = "17",
doi = "10.1073/pnas.151260298",
language = "English (US)",
volume = "98",
pages = "8480--8484",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

TY - JOUR

T1 - Antibodies with infinite affinity

AU - Chmura, A. J.

AU - Orton, M. S.

AU - Meares, C. F.

PY - 2001/7/17

Y1 - 2001/7/17

N2 - Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, we engineered complementary reactive groups in the antibody binding pocket and the ligand, so that they would be in close proximity in the antibody/ligand complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are very large, allowing a covalent reaction to link the two together. By eliminating the dissociation of the ligand from the antibody, we have made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs.

AB - Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, we engineered complementary reactive groups in the antibody binding pocket and the ligand, so that they would be in close proximity in the antibody/ligand complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are very large, allowing a covalent reaction to link the two together. By eliminating the dissociation of the ligand from the antibody, we have made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs.

UR - http://www.scopus.com/inward/record.url?scp=0035902463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035902463&partnerID=8YFLogxK

U2 - 10.1073/pnas.151260298

DO - 10.1073/pnas.151260298

M3 - Article

C2 - 11447282

AN - SCOPUS:0035902463

VL - 98

SP - 8480

EP - 8484

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 15

ER -