Anti-Methamphetamine [6H4 S93T]

Absolute Antibody

Anti-Methamphetamine [6H4 S93T]

9

This antibody is capable of recognizing methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 4-OH-METH. Methamphetamine is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly a

This antibody is an affinity improved version of antibody 6H4 that has a 3.1 fold enhancement in affinity for METH and 26 fold for AMP (PMID: 24419156). The original IgG1 version of 6H4 antibody binds methamphetamine with a binding affinity of Kd=11nM. The initial binding characterization of this antibody was done using ELISA (US7858756). The scFv version of this antibody was reported to bind (+)-METH with a binding affinity of kd=10nM. The binding affinity of the scFv version 6H4 for METH and similar drugs was determined by bead-based radioimmunoassay (RIA) (PMID: 18192498). To test the in vivo efficacy of the scFv6H4, male Sprague Dawley rats were implanted with 3-day sc osmotic pumps delivering 3.2 mg/kg/day METH. The scFv was stable for an extended period of time in vivo and was able to significantly redistribute METH into serum for at least 4 hrs. PCKN data suggested that the multivalent forms of scFv6H4 were primarily responsible for the longer term METH binding in serum, even though the scFv6H4 dose was primarily composed of monomer (75%) (PMID: 18192498). The scFv version of this antibody was also used in the generation of an adeno-associated viral (AAV)-delivered DNA sequence for a single-chain variable fragment or AAV8 scFv construct for long term continuous expression of anti-METH antibody fragments in mice. Mice expressed each scFv for at least 212 days, achieving micromolar scFv concentrations in serum. The circulating scFvs were capable of decreasing brain METH concentrations by up to 60% and sequestering METH in serum for 2 to 3 hrs. (PMID: 29958300). The crystal structure revealed that scFv6H4 binds to METH and MDMA in a deep pocket that almost completely encases the drugs mostly through aromatic interactions. In addition, the cationic nitrogen of METH and MDMA forms a salt bridge with the carboxylate group of a glutamic acid residue and a hydrogen bond with a histidine side chain. There are two water molecules in the binding pocket and one of them is positioned for a C-HO interaction with the aromatic ring of METH (PMID: 19760665).

ELISA, RadioImmunoAssay

Research Use Only

Monoclonal

6H4 S93T

Human

IgG1

This chimeric human antibody was made using the variable domain sequences of the original Mouse IgG1 format for improved compatibility with existing reagents assays and techniques.

Other Species

-20°C,2°C to 8°C

12352203