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Extended Length Heterobifunctional Coupling Agents for Protein Conjugations
- Source :
- Bioconjugate Chemistry. 7:88-95
- Publication Year :
- 1996
- Publisher :
- American Chemical Society (ACS), 1996.
-
Abstract
- A series of extended length heterobifunctional coupling agents is described. The successive aminocaproic acid homologation of succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate, a known 9-atom long maleimide active ester linker, yielded 16-, 23-, and 30-atom long maleimide active ester homologues. The performance study of these coupling agents in automated microparticle enzyme immunoassays showed that, in the alpha fetoprotein assay, in which the linkers were employed in the construction of the alkaline phosphatase-antibody conjugates, the signal increased 64% when the length of the linker was incremented from 9 atoms to 23 atoms and 82% for the 30-atom long linker as compared with the 9-atom homologue. Similar improvements were observed in the performance of carbohydrate antigen, marker of ovarian cancer (CA-125), immunoassay where the linkers were used for conjugation of the capture antibody anti-CA-125 to the microparticle. Thus, a 300% signal improvement resulted when a 30-atom linker was used instead of the 9-atom homologue. The observed differences in the performance of the conjugates are interpreted as resulting from improved antibody binding and lowering of the steric hindrance of the complementarity-determined region of the antibody when longer coupling agents were used.
- Subjects :
- Stereochemistry
Biomedical Engineering
Pharmaceutical Science
Bioengineering
Spectrometry, Mass, Fast Atom Bombardment
Antibodies
Maleimides
Structure-Activity Relationship
chemistry.chemical_compound
medicine
Animals
Microparticle
Maleimide
Immunoassay
Pharmacology
medicine.diagnostic_test
Chemistry
Organic Chemistry
Antibodies, Monoclonal
Proteins
Alkaline Phosphatase
Coupling (electronics)
Cross-Linking Reagents
CA-125 Antigen
Immunoglobulin G
Cattle
alpha-Fetoproteins
Enzyme immunoassays
Aminocaproic acid
Linker
Biotechnology
Conjugate
medicine.drug
Subjects
Details
- ISSN :
- 15204812 and 10431802
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Bioconjugate Chemistry
- Accession number :
- edsair.doi.dedup.....fe41e2b9e963cc2d872a3bea0f3ce75e
- Full Text :
- https://doi.org/10.1021/bc950080+