ArticleScientific reports2014
Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- A Highly Sensitive Detection System based on Proximity-dependent Hybridization with Computer-aided Affinity Maturation of a scFv Antibody.Scientific reports · 2018Article
- Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse.PloS one · 2018Article
- A mathematical model of a recombinant humanized anti-cocaine monoclonal antibody's effects on cocaine pharmacokinetics in mice.Life sciences · 2017Article
- Sphinx: merging knowledge-based and ab initio approaches to improve protein loop prediction.Bioinformatics (Oxford, England) · 2017Article
- How B-Cell Receptor Repertoire Sequencing Can Be Enriched with Structural Antibody Data.Frontiers in immunology · 2017Review
- Antibody H3 Structure Prediction.Computational and structural biotechnology journal · 2017Review
- PEGylation of a High-Affinity Anti-(+)Methamphetamine Single Chain Antibody Fragment Extends Functional Half-Life by Reducing Clearance.Pharmaceutical research · 2016Article
- Successful engineering of a highly potent single-chain variable-fragment (scFv) bispecific antibody to target disialoganglioside (GD2) positive tumors.Oncoimmunology · 2016Article
- A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments.Scientific reports · 2015Article
- Article
- Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases.Expert review of anti-infective therapy · 2015Review
- A tool kit for rapid cloning and expression of recombinant antibodies.Scientific reports · 2014Article
- Simultaneous affinity maturation and developability enhancement using natural liability-free CDRs.mAbsArticle
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Methamphetamine (METH) abuse is a worldwide threat, without any FDA approved medications. Anti-METH IgGs and single chain fragments (scFvs) have shown efficacy in preclinical studies. Here we report affinity enhancement of an anti-METH scFv for METH and its active metabolite amphetamine (AMP), through the introduction of point mutations, rationally designed to optimize the shape and hydrophobicity of the antibody binding pocket. The binding affinity was measured using saturation binding technique. The mutant scFv-S93T showed 3.1 fold enhancement in affinity for METH and 26 fold for AMP. The scFv-I37M and scFv-Y34M mutants showed enhancement of 94, and 8 fold for AMP, respectively. Structural analysis of scFv-S93T:METH revealed that the substitution of Ser residue by Thr caused the expulsion of a water molecule from the cavity, creating a more hydrophobic environment for the binding that dramatically increases the affinities for METH and AMP.
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Registered trials
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.