Target-selective photo-degradation of verotoxin-1 and reduction of its cytotoxicity to Vero cells using porphyrin-globotriose hybrids.

Designed and synthesized porphyrin-globotriose hybrids effectively degraded verotoxin-1, which causes severe bloody diarrhoea and fetal hemolytic uremic syndrome (HUS). Degradation was achieved using long-wavelength UV or visible light irradiation in the absence of any additives and under neutral conditions. Moreover, the hybrids neutralized the cytotoxicity of verotoxin upon photo-irradiation.

Photodegradation and inhibition of drug-resistant influenza virus neuraminidase using anthraquinone-sialic acid hybrids.

The anthraquinone-sialic acid hybrids designed effectively degraded not only non-drug-resistant neuraminidase but also drug-resistant neuraminidase, which is an important target of anti-influenza therapy. Degradation was achieved using long-wavelength UV radiation in the absence of any additives and under neutral conditions. Moreover, the hybrids efficiently inhibited neuraminidase activities upon photo-irradiation.

Chemical methods for degradation of target proteins using designed light-activatable organic molecules.

Molecular design, chemical synthesis, and biological evaluation of several designed organic molecules, which target-selectively degrade proteins upon photo-irradiation, are introduced. The designed molecules for protein photo-degradation include 2-phenylquinoline-steroid hormone hybrids and porphyrin derivatives, both of which selectively photo-degrade estrogen receptor-α, and fullerene-sugar and -sulfonic acid hybrids, which selectively photo-degrade HIV-1 protease and amyloid β, respectively. The information will provide a novel and effective way to control specific functions of proteins, and contribute to the molecular design of novel protein photo-degrading agents, which should find wide application in chemistry, biology, and medicine.

Molecular design, chemical synthesis, and biological evaluation of agents that selectively photo-degrade the transcription factor estrogen receptor-α.

2-Phenylquinoline (1) degraded proteins under photo-irradiation with long-wavelength UV light without additives and under neutral conditions. We designed and synthesized a 2-phenylquinoline-estrogen receptor-α (ER-α) agonist (hybrid 2) and a 2-phenylquinoline-ER-α antagonist (hybrid 3) containing estradiol and 4-hydroxytamoxifen moieties, respectively. These 2-phenylquinoline hybrids effectively and selectively photo-degraded the target transcription factor, ER-α, which has a high affinity for estradiol and 4-hydroxytamoxifen.

Target-selective degradation of cancer-related proteins by novel photosensitizers for molecular-targeted photodynamic therapy.

Proteins are key players in many biological events including cancers. The development of novel photosensitizers for the selective degradation of cancer-related proteins has attracted much attention in the fields of photodynamic therapy for various cancers. In this review article, several novel photosensitizers, which selectively degrade cancer-related proteins under photoirradiation and mild conditions without any further additives, are introduced.

Target-selective photo-degradation of HIV-1 protease by a fullerene-sugar hybrid.

A designed fullerene-sugar hybrid effectively and selectively degraded the target protein, HIV-1 protease, which has high affinity for the fullerene moiety; degradation was achieved using long-wavelength UV or visible photo-irradiation, in the absence of any additives and under neutral conditions.

Target-selective degradation of proteins by porphyrins upon visible photo-irradiation.

A porphyrin derivative effectively and selectively degraded the target transcription factor, human estrogen receptor-alpha (hER-alpha), upon visible light irradiation, in the absence of additives and under neutral conditions.