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A few small molecules isolated from a fruit block the activity of a malfunctioning enzyme that modifies histone protein, which with DNA makes chromatin, the building block of chromosomes,

researchers have found1. Known as histone acetyltransferase (HAT), the enzyme's altered function leads to faulty expressions of gene and protein synthesis resulting in diseases like

Huntington disease, cardiac diseases, diabetes, AIDS and even cancer. Given its implications in so many diseases, HAT has emerged as a coveted drug target. For the study, the researchers

isolated garcinol, a complex organic compound from Garcinia indica, a fruit tree popularly known as Kokam. They synthesized two more molecules – isogarcinol (IG) and LTK14 – from garcinol.

The researchers tested their inhibitory activity against a specific HAT enzyme known as p300. All the three molecules inhibited the activity of p300 in a concentration dependent manner. The

molecules also altered the enzyme structure. The research reveals that LTK14 is non-toxic and specific to a given target like p300 compared to garcinol, which is highly toxic and

non-specific. From the therapeutic point of view, toxicity is of great concern no matter what the potency. At the same time non-specific inhibitory nature of garcinol may lead to many off

target effects deleterious to healthy cells. "We have also shown that LTK14 does not kill the human T-cell, a type of white blood cell but dramatically represses the multiplication of

HIV, targeting p300," says lead researcher Tapas Kundu. LTK14 can be a useful tool in probing p300, which is involved in diverse cellular processes, he concludes. The authors of this

work are from: _Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, India; Biophysics

Division, I/AF, Saha Institute of Nuclear Physics, Bidhannagar, Kolkata, India & Institute of Bioinformatics and Applied Biotechnology, International Technology Park Bangalore (ITPB),

Whitefield Road, Bangalore, India. _