Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity

Katherine E. Larrimore, Matthew Barcus, Latha Kannan, Yang Gao, Chang Guo Zhan, William Stephen Brimijoin, Tsafrir Mor

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties.

Original languageEnglish (US)
Pages (from-to)217-220
Number of pages4
JournalChemico-Biological Interactions
Volume203
Issue number1
DOIs
StatePublished - Mar 25 2013

Fingerprint

Butyrylcholinesterase
Hydrolases
Cocaine
Recurrence
Cocaine-Related Disorders
Street Drugs
Pathogens
Enzymes
Reward
Viruses
Patient rehabilitation
Tobacco
Catalyst activity
Brain
Rehabilitation
Therapeutics
Serum
Pharmaceutical Preparations
Proteins

Keywords

  • Addiction
  • Drug abuse
  • Plant biotechnology
  • Protein engineering

ASJC Scopus subject areas

  • Toxicology

Cite this

Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity. / Larrimore, Katherine E.; Barcus, Matthew; Kannan, Latha; Gao, Yang; Zhan, Chang Guo; Brimijoin, William Stephen; Mor, Tsafrir.

In: Chemico-Biological Interactions, Vol. 203, No. 1, 25.03.2013, p. 217-220.

Research output: Contribution to journalArticle

Larrimore, Katherine E. ; Barcus, Matthew ; Kannan, Latha ; Gao, Yang ; Zhan, Chang Guo ; Brimijoin, William Stephen ; Mor, Tsafrir. / Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity. In: Chemico-Biological Interactions. 2013 ; Vol. 203, No. 1. pp. 217-220.
@article{d4de8150463a47e58aea0204b9cca166,
title = "Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity",
abstract = "Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80{\%} chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties.",
keywords = "Addiction, Drug abuse, Plant biotechnology, Protein engineering",
author = "Larrimore, {Katherine E.} and Matthew Barcus and Latha Kannan and Yang Gao and Zhan, {Chang Guo} and Brimijoin, {William Stephen} and Tsafrir Mor",
year = "2013",
month = "3",
day = "25",
doi = "10.1016/j.cbi.2012.09.004",
language = "English (US)",
volume = "203",
pages = "217--220",
journal = "Chemico-Biological Interactions",
issn = "0009-2797",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity

AU - Larrimore, Katherine E.

AU - Barcus, Matthew

AU - Kannan, Latha

AU - Gao, Yang

AU - Zhan, Chang Guo

AU - Brimijoin, William Stephen

AU - Mor, Tsafrir

PY - 2013/3/25

Y1 - 2013/3/25

N2 - Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties.

AB - Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties.

KW - Addiction

KW - Drug abuse

KW - Plant biotechnology

KW - Protein engineering

UR - http://www.scopus.com/inward/record.url?scp=84875808177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875808177&partnerID=8YFLogxK

U2 - 10.1016/j.cbi.2012.09.004

DO - 10.1016/j.cbi.2012.09.004

M3 - Article

C2 - 23000451

AN - SCOPUS:84875808177

VL - 203

SP - 217

EP - 220

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

IS - 1

ER -