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Immucillins in Infectious Diseases.

Gary B Evans1, Peter C Tyler1, Vern L Schramm2

  • 1Ferrier Research Institute, Victoria University of Wellington , 69 Gracefield Road, Gracefield, Lower Hutt, 5010, New Zealand.

ACS Infectious Diseases
|November 21, 2017
PubMed
Summary

Immucillins, stable analogues mimicking transition states, show promise for infectious diseases. They target essential enzymes in malaria, H. pylori, and viral infections, with some already in clinical trials.

Keywords:
DADMe-Immucillin-GImmucillin-ARNA chain terminationRNA-dependent RNA polymeraseantiviralsfutalosine pathwaymalaria antibioticsmethylthioadenosine phosphorylasepurine nucleoside phosphorylasepurine-less deathspecies specific antibiotics

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Area of Science:

  • Biochemistry and Medicinal Chemistry
  • Infectious Diseases and Parasitology
  • Antiviral and Antibacterial Therapeutics

Background:

  • Infectious agents utilize ribosyltransferase chemistry for essential metabolic pathways.
  • Immucillins are stable analogues designed to mimic transition states of N-ribosyltransferase enzymes.
  • Targeting parasite-specific enzymes offers a strategy for selective antimicrobial development.

Purpose of the Study:

  • To review the application of Immucillins against three distinct infectious agents.
  • To highlight the therapeutic potential of Immucillins in treating malaria, Helicobacter pylori infections, and viral diseases.
  • To discuss the clinical progress and future development of Immucillins for infectious disease applications.

Main Methods:

  • Review of existing literature on Immucillin analogues and their mechanisms of action.
  • Focus on DADMe-Immucillin-G as a purine nucleoside phosphorylase (PNP) inhibitor for Plasmodium falciparum.
  • Examination of methylthioadenosine nucleosidase (MTAN) inhibitors for Helicobacter pylori and Immucillin-A as an antiviral agent.

Main Results:

  • DADMe-Immucillin-G effectively inhibits purine salvage in Plasmodium falciparum, leading to cell death.
  • MTAN inhibitors show high specificity against Helicobacter pylori, sparing beneficial gut microbiota.
  • Immucillin-A acts as a prodrug, becoming an antiviral agent by terminating viral RNA synthesis.

Conclusions:

  • Immucillins demonstrate significant potential as therapeutics for diverse infectious diseases.
  • Targeted inhibition of parasite and bacterial enzymes offers a route to selective antimicrobial drugs.
  • Clinical trial successes in other areas support the broader development of Immucillins for infectious disease treatment.