Selection and analysis of a DNA aptamer binding α-amanitin from Amanita phalloides.

Mushroom foraging is very popular in some regions of the world. Sometimes toxic and edible mushrooms are mistaken by mushroom collectors, leading to serious human poisoning. The group of mushrooms highly dangerous for human health includes Amanita phalloides.

Antibody-drug conjugate payloads.

Toxin payloads, or drugs, are the crucial components of therapeutic antibody-drug conjugates (ADCs). This review will give an introduction on the requirements that make a toxic compound suitable to be used in an antitumoral ADC and will summarize the structural and mechanistic features of four drug families that yielded promising results in preclinical and clinical studies.

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology.

Phallotoxins inhibit the dynamics of microfilaments in cells and lead to apoptosis. Due to poor cellular uptake these effects cannot be studied in live cells, even at millimolar toxin concentrations, nor can phalloidin be used for the elimination of tumor cells. Uptake is greatly enhanced by conjugation of phallotoxins to either lipophilic or polycationic moieties, such as oleic acid, polylysine, or Tat-peptide.

Therapeutic potential of amanitin-conjugated anti-epithelial cell adhesion molecule monoclonal antibody against pancreatic carcinoma.

Background: Human epithelial cell adhesion molecule (EpCAM) is overexpressed in many cancers. Anti-EpCAM antibodies have shown promise in preclinical studies, but showed no tumor regression in a recent phase II clinical trial. Therefore, we generated a novel anti-EpCAM antibody-drug conjugate and assessed whether it showed enhanced antitumor effects.

Molecular characterization and inhibition of amanitin uptake into human hepatocytes.

Amatoxins are the main poison of the green death cap (Amanita phalloides) and among the most dangerous natural toxins causing hepatic failure. A possible therapeutic approach is the inhibition of the transporting systems mediating the uptake of amatoxins into human hepatocytes, which, however, have yet to be identified. In the current study we tested whether members of the organic anion-transporting polypeptide (OATP) family, localized in the sinusoidal membranes of human hepatocytes, are involved in amatoxin uptake.

Identification of phalloidin uptake systems of rat and human liver.

To determine whether the liver toxin phalloidin is transported into hepatocytes by one of the known bile salt transporters, we expressed the sodium-dependent Na+/taurocholate cotransporting polypeptide (Ntcp) and several sodium-independent bile salt transporters of the organic anion transporting polypeptide (OATP/SLCO) superfamily in Xenopus laevis oocytes and measured uptake of the radiolabeled phalloidin derivative [3H]demethylphalloin. We found that rat Oatp1b2 (previously called Oatp4 (Slc21a10)) as well as human OATP1B1 (previously called OATP-C (SLC21A6)) and OATP1B3 (previously called OATP8 (SLC21A8)) mediate uptake of [3H]demethylphalloin when expressed in X. laevis oocytes.

Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins.

Phalloidin, the major phallotoxin of the mushroom Amanita phalloides, enters hepatocytes by a carrier-mediated mechanism. The molecular identity of the transport proteins mediating phalloidin uptake was so far unknown. Earlier studies in rat liver indicated that phalloidin may share a common mechanism of uptake with organic anions like bile salts.