Concept

Biocrystallization

Biocrystallization is the formation of crystals from organic macromolecules by living organisms. This may be a stress response, a normal part of metabolism such as processes that dispose of waste compounds, or a pathology. Template mediated crystallization is qualitatively different from in vitro crystallization. Inhibitors of biocrystallization are of interest in drug design efforts against lithiasis and against pathogens that feed on blood, since many of these organisms use this process to safely dispose of heme. Under severe stress conditions the bacteria Escherichia coli protects its DNA from damage by sequestering it within a crystalline structure. This process is mediated by the stress response protein Dps and allows the bacteria to survive varied assaults such as oxidative stress, heat shock, ultraviolet light, gamma radiation and extremes of pH. Blood feeding organisms digest hemoglobin and release high quantities of free toxic heme. To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin. To date, the only definitively characterized product of hematin disposal is the pigment hemozoin. Hemozoin is per definitionem not a mineral and therefore not formed by biomineralization. Heme biocrystallization has been found in blood feeding organisms of great medical importance including Plasmodium, Rhodnius and Schistosoma. Heme biocrystallization is inhibited by quinoline antimalarials such as chloroquine. Targeting heme biocrystallization remains one of the most promising avenues for antimalarial drug development because the drug target is highly specific to the malarial parasite, and outside the genetic control of the parasite. Lithiasis (formation of stones) is a global human health problem. Stones can form in both urinary and gastrointestinal tracts. Related to the formation of stones is the formation of crystals; this can occur in joints (e.g. gout) and in the viscera.

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Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanopartides that mimic functional components of ...
AMER CHEMICAL SOC2022

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Related concepts (6)
Hemozoin
Haemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as malaria parasites (Plasmodium spp.), Rhodnius and Schistosoma digest haemoglobin and release high quantities of free heme, which is the non-protein component of haemoglobin. Heme is a prosthetic group consisting of an iron atom contained in the center of a heterocyclic porphyrin ring. Free heme is toxic to cells, so the parasites convert it into an insoluble crystalline form called hemozoin.
Chloroquine
Infobox drug | Watchedfields = changed | verifiedrevid = 459442331 | drug_name = | INN = | type = | image = Chloroquine.svg | width = 200 | alt = | image2 = Chloroquine-ligand-CLQ-A-from-PDB-xtal-4FGL-Mercury-3D-balls.png | width2 = 180 | alt2 = | caption = | pronounce = ˈklɔːrəkwiːn | tradename = Aralen, other | Drugs.
Plasmodium falciparum
Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer (Burkitt's lymphoma) and is classified as a Group 2A (probable) carcinogen.
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