Evidence map›Paper›PMID 17084858›Full record

ArticleJournal of molecular biology2007

Identification and characterization of single chain anti-cocaine catalytic antibodies.

Kathleen M McKenzie, Jenny M Mee, Claude J Rogers, Mark S Hixon, Gunnar F Kaufmann, Kim D Janda

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Catalytic Antibody Blunts Carfentanil-Induced Respiratory Depression.ACS pharmacology & translational science · 2023
    Article
  2. Review
  3. Review
  4. Vaccines against drugs of abuse: where are we now?Therapeutic advances in vaccines · 2014
    Review
  5. Future pharmacological treatments for substance use disorders.British journal of clinical pharmacology · 2014
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Immunopharmacotherapeutic manifolds and modulation of cocaine overdose.Pharmacology, biochemistry, and behavior · 2011
    Article
  11. Article
  12. Article
  13. Anti-cocaine vaccine development.Expert review of vaccines · 2010
    Review
  14. Article
  15. Article
  16. Review
  17. A cocaine hydrolase engineered from human butyrylcholinesterase selectively blocks cocaine toxicity and reinstatement of drug seeking in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2008
    Article
  18. Antibody-mediated prevention of Fusarium mycotoxins in the field.International journal of molecular sciences · 2008
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Kathleen M McKenzieDepartments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, La Jolla, CA 92037, USA.
Jenny M Mee
Claude J Rogers
Mark S Hixon
Gunnar F Kaufmann
Kim D Janda
Scripps Research Institute · US

Funding

Immunopharmacotherapy for the Treatment of Cocaine AbuseR01DA008590 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI JANDA, KIM · 1994 to 2016
$6.4M
Catalytic Antibodies as Therapy for Drug AddictionR01DA015700 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI JANDA, KIM D. · 2003 to 2006
$1.7M
Cocaine degradation: Improving antibody efficacyF32DA018024 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI MCKENZIE, KATHLEEN M · 2005 to 2006
$98k
NIDA NIH HHS DA 08590NIDA NIH HHS DA 15700NIDA NIH HHS DA 18024NIDA NIH HHS F32 DA018024NIDA NIH HHS R01 DA008590NIDA NIH HHS R01 DA015700
6 · The paper itself

Abstract

Cocaine is a powerful and addictive stimulant whose abuse remains a prevalent health and societal crisis. Unfortunately, no pharmacological therapies exist and therefore alternative protein-based therapies have been examined. One such approach is immunopharmacotherapy, wherein antibodies are utilized to either bind or hydrolyze cocaine thereby blocking it from exerting its euphoric effect. Towards this end, antibodies capable of binding and hydrolyzing cocaine were identified by phage display from a biased single chain antibody library generated from the spleens of mice previously immunized with a cocaine phosphonate transition state analog hapten. Two classes of antibodies emerged based on sequence homology and mode of action. Alanine scanning mutagenesis and kinetic analysis revealed that residues H97, H99, and L96 are crucial for antibodies 3F5 and 3H9 to accelerate the hydrolysis of cocaine. Antibodies 3F1 through 3F4, which are similar to our previously identified 3A6 class of antibodies, catalyze hydrolysis through transition state stabilization by tyrosine or histidine residues H50 and L94. Mutation of either one or both tyrosine residues to histidine conferred hydrolytic activity on previously inactive antibody 3F4. Mutational analysis of residue H50 of antibody 3F3 resulted in a glutamine mutant with a rate enhancement three times greater than wild-type. A double mutant, containing glutamineH50 and lysineH52, showed a tenfold rate enhancement over wild-type. These results indicate the power of initial selection of catalytic antibodies from a biased antibody library in both rapid generation and screening of mutants for improved catalysis.

Indexed as

AlanineAmino Acid SequenceAnimalsAntibodies, CatalyticCocaineComplementarity Determining RegionsDNA Mutational AnalysisEstersHydrolysisKineticsMiceMolecular Sequence DataMutant ProteinsMutationSequence AlignmentAlanineAntibodies, CatalyticCocaineComplementarity Determining RegionsEstersMutant Proteins

Identifiers

PMID17084858
PMCPMC1828637
OpenAlexW1975485717

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.