Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering
作者： Shraddha Thakkar , Nisha Nanaware-Kharade , Reha Celikel , Eric C. Peterson , Kottayil I. Varughese
DOI: 10.1038/SREP03673
关键词:
摘要: 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 its active metabolite amphetamine (AMP), through the introduction point mutations, rationally designed to optimize shape hydrophobicity antibody binding pocket. The was measured using saturation technique. mutant scFv-S93T showed 3.1 fold 26 AMP. scFv-I37M scFv-Y34M mutants 94, 8 AMP, respectively. Structural analysis scFv-S93T:METH revealed that substitution Ser residue by Thr caused expulsion water molecule from cavity, creating more hydrophobic environment dramatically increases affinities
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