A key component of the quality of pharmaceutical drugs is the control of
impurities. It is important to identify and quantify levels of impurities that may
be present to provide safe, effective and well-controlled medicines. The measurement
and identification of impurities to today’s standards presents significant
challenges to the analytical chemist.
Many physiologically important proproteins, pathogenic bacterial exo-toxins and viral envelope glycoproteins are activated by the proprotein con-vertase furin, which makes furin inhibitor a hot target for basic research
and drug design. Although synthetic and bioengineered inhibitors of furin
have been well characterized, its endogenous inhibitor has not been directly
purified from mammalian tissues to date.
Pseudomonasexotoxin A (PE) is a highly toxic protein secreted by the
opportunistic pathogen Pseudomonas aeruginosa. The modular structure
and corresponding mechanism of action of PE make it amenable to exten-sive modifications that can redirect its potent cytotoxicity from disease to a
Hydrogen sulfide is a potent toxin of aerobic respiration, but also has
physiological functions as a signalling molecule and as a substrate for ATP
production. A mitochondrial pathway catalyzing sulfide oxidation to thio-sulfate in three consecutive reactions has been identified in rat liver as well
as in the body-wall tissue of the lugworm,Arenicola marina.
Okadaic acid (OA) and its analogs, the dinophysistoxins, are potent inhibi-tors of protein phosphatases 1 and 2A. This action is well known to cause
diarrhea and gastrointestinal symptons when the toxins reach the digestive
tract by ingestion of mollusks. A less well-known effect of these group of
toxins is their effect in the cytoskeleton.
The lugwormArenicola marinainhabits marine sediments in which sulfide
concentrations can reach up to 2 mm. Although sulfide is a potent toxin
for humans and most animals, because it inhibits mitochondrial cyto-chromec oxidase at micromolar concentrations,A. marinacan use elec-trons from sulfide for mitochondrial ATP production.
Harrison's Internal Medicine Chapter 134. Botulism
Definition Botulism is a paralytic disease caused by potent protein neurotoxins elaborated by Clostridium botulinum. Illness begins with cranial nerve
involvement and proceeds caudally to involve the extremities. Cases may be classified as (1) food-borne botulism, from ingestion of preformed toxin in food contaminated with C.
Botulism is a paralytic disease caused by potent protein neurotoxins elaborated by Clostridium botulinum. Illness begins with cranial nerve involvement and proceeds caudally to involve the extremities. Cases may be classified as (1) food-borne botulism, from ingestion of preformed toxin in food contaminated with C. botulinum; (2) wound botulism, from toxin produced in wounds contaminated with the organism; and (3) intestinal botulism, from ingestion of spores and production of toxin in the intestine of infants (infant botulism) or adults.
The botulinum neurotoxins (BoNTs) are the most potent protein toxins for
humans. There are seven serotypes of BoNTs (A–G), based on a lack of
cross-antiserum neutralization. The BoNT⁄C and BoNT⁄D serotypes
include mosaic toxins that are organized as D–C and C–D toxins.
a-Conotoxins from marine snails are known to be selective and potent
competitive antagonists of nicotinic acetylcholine receptors. Here we des-cribe the purification, structural features and activity of two novel toxins,
SrIA and SrIB, isolated fromConus spuriuscollected in the Yucatan Chan-nel, Mexico.
Bacillus cereusisolated from the larvae of Myrmeleon bore
was found to secrete proteins that paralyze and kill German
cockroaches, Blattela germanica, when injected. One of
these active proteins was purified from the culture broth
ofB.cereususing anion-exchange and gel-filtration chro-matography. The purified toxin, with a molecular mass of
34 kDa, was identified as sphingomyelinase C (EC126.96.36.199)
on the basis of its N-terminal and internal amino-acid
sequences. A recombinant sphingomyelinase C expressed in
Escherichia coliwas as potent as the native protein in killing
There is much evidence to indicate that cholesterol forms
lateral membranemicrodomains (rafts), and to suggest their
important role in cellular signaling. However, no probe has
been produced to analyze cholesterol behavior, especially
cholesterol movement in rafts, in real time. To obtain a
potent tool for analyzing cholesterol dynamics in rafts, we
prepared and characterized several truncated fragments of
h-toxin (perfringolysin O), a cholesterol-binding cytolysin,
whose chemicallymodified formhas been recently shown to
bind selectively to rafts. ...
Ricin is a heterodimeric plant protein that is potently toxic to mammalian
cells. Toxicity results from the catalytic depurination of eukaryotic ribo-somes by ricin toxin A chain (RTA) tBáo cáo khoa học: The isolation and characterization of temperature-dependehat follows toxin endocytosis to, and
translocation across, the endoplasmic reticulum membrane.
Several protein toxins, such as the potent plant toxin ricin, enter mamma-lian cells by endocytosis and undergo retrograde transport via the Golgi
complex to reach the endoplasmic reticulum (ER). In this compartment the
catalytic moieties exploit the ER-associated degradation (ERAD) pathway
to reach their cytosolic targets. Bacterial toxins such as cholera toxin or
Pseudomonasexotoxin A carry KDEL or KDEL-like C-terminal tetrapep-tides for efficient delivery to the ER.