Thursday, December 25, 2008

Nobel Prize in Chemistry 2008: Who won it and why?

Nobel Prize for Chemistry 2008 to Osamu Shimomura (USA), Martin Chalfie (USA) and Roger Y. Tsien (USA) for the "discovery and development of the green fluorescent protein, GFP". If interested watch the BBC documentary.

A new experimental drug "antagomir" (antisense oligonucleotide) as an anti- miR-21 agent..

MicroRNAs are small scraps of RNA comprising around 20 nucleotides and it is only recently that scientists have discovered their power which is they can regulate the expression (switching on and off) of a large number of human genes (they are like "master controllers"). And also these are the culprits (when microRNAs don't appear in the right place at the right time within cells) for diseases such as cancer, viral infections, inflammatory diseases and metabolic disorders. The potential to use them as targets for drugs is obvious and possibly explains why this is one of the fastest growing areas of development for new drugs and treatments.

Scientists already knew that microRNA was involved in switching genes on and off in the heart, but the underlying mechanisms and how they relate to the development of particular types of heart disease and their potential as drug targets were still relatively unknown.

Thum and colleagues discovered that miR-21 was expressed in the heart's fibroblast cells (cells that make the scaffolding of collagen or connective tissue that hold the shape of the organ) and were in greater numbers in lab mice bred to have heart failure and also in human tissue from patients who had heart failure.

In this study they showed that increasing expression of miR-21 changed the way that signals behaved in a previously unknown stress response pathway that involved the gene sprouty-1 and the MAP-kinase signaling pathway. In turn, increasing the activity of the MAP-kinase pathway led to a number of signs of heart failure, such as enhanced fibroblast survival, increased secretion of factors like fibroblast growth factor, tissue scarring (fibrosis), and cardiac dysfunction including cellular hypertrophy.

The researchers proved they could administer anti-miR-21 effectively to the heart by monitoring it with fluorescence staining. Then, in a mouse transaortic constriction model of human heart failure, they showed that anti-miR-21 silenced increased expression of miR-21 and corrected downstream changes in sprouty-1 and MAP-kinase signaling.

The interesting thing is their conclusion : Anti-miR-21, showed the most statistically significant improvement in the heart failure mouse model when given before induction of heart failure and for as long as three weeks afterward and it might be possible to target entire disease pathways with one drug. Contrats Dr. Thomas Thum.


Sunday, December 21, 2008

A Deep Insight into the World Gene Therapy Market

A new market research report related to the Biotechnologies and Genetics industry about the trends in "antisense drugs".....

Non ulcerogenic new antiinflammatory drugs ?

When we see the presently available NSAIDs, most of them have ulcerogenicity as one of the common side effect. Ulcerogenicity can be explained by the metabolism of Arachidonic acid into various metabolites. Most of the drugs (NSAIDs) act by inhibiting the prostaglandins. But some of the prostaglandins are essential as cytoprotective layer and hence selective inhibitors of Cyclooxygenase –II (COX-II) and 5-LO (Lipoxygenase) are better tolerable and hence we can call these drugs as non ulcerogenic NSAIDs. Though these 2 enzymes (COX-II and 5-LO) were the targets of many drug discovers (as for as my knowledge goes, 1996-98 there were many papers regarding the selective inhibitors).

Now Oliver Werz and co workers have come with some new compounds 2-(4-(biphenyl-4-ylmethylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (with some structural variations like ╬▒ substitution with extended n-alkyl or bulky aryl substituents and concomitant replacement of the 2,3-dimethylaniline by a biphenyl-4-yl-methane-amino residue) a derivative of pirinixic acid [PA, 2-(4-chloro-6-(2,3-dimethylphenylamino) pyrimidin-2-ylthio)acetic acid.

Significance of this research is the, less pronounced inhibition of cyclooxygenases-1/2. Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacologial profile and a potential for therapeutic use. More……

Iron complex mimics soil bacteria .....

Is there any synthetic chemical that acts, like a soil bacteria and there by degrade the aromatic compounds?. Now Prof. Lawrence Jr., and his group has come out with an interesting “synthetic non-heme iron complex “-that is able to catalyse the reaction.

The natural method for the degradation of aromatic compounds starts with the cis-dihydroxylation of an aromatic double bond by non-heme iron enzymes and the best known of these enzymes is naphthalene 1,2-dioxygenase (NDO), which catalyses the conversion of naphthalene to cis-(1R,2S)-1,2-dihydro-1,2-naphthalenediol. Although catalysts, those able to cis-hydroxylate olefin double bonds are known, the significance of this research is that a “synthetic catalyst which could carry out the same reaction on aromatic double bonds”.

Prof. Que, used a complex which had previously been successful in the cis-dihydroxylation of olefins, [FeII(TPA)(NCMe)2](OTf)2 [where TPA = tris(2-pyridylmethylamine)], using H2O2 as the oxidant. Interestingly the major of the identified four products (cis-diol), is identical to that produced in the enzyme-catalysed reaction. They also carried out mechanistic studies and found that the process is assisted by water. Though further studies are essential to substantiate the biomimetic catalysis of oxidations (previously carried out by enzymes). Hope this research will have its influence, in the areas like drug discovery, synthetic chemistry and environment issues…..

Saturday, December 20, 2008

How Genes and Proteins Interact……

If we think back how, the killer illnesses such as cancer and Alzheimer's begin and are they anything to do with fundamental mechanisms of epigenetic control ? Dr. Stephen Michnick and group says, "control of genes is subject to both inherited and environmental factors, so that genes may be read differently and up to what a person eats or even what their grandmother ate” - something we all, try to find comparisons between our children with our parents.

In the PLoS study, the researchers identified proteins they described as gene grammarians. Gene grammarians are linked to a larger complex of proteins that determine whether a gene can be read – or not – based on DNA structure. The scientists found gene grammarians can determine whether cells have different functions and can identify the different levels of susceptibility – or resistance – individuals could have to specific diseases.

The study provides insight into the fundamental mechanisms of epigenetic control – gene expression that are controlled by heritable but potentially reversible changes in DNA – which provides a new avenue towards understanding environmental effects on the human genome and I hope this study will have some impact on genetically transmitted deceases……

Friday, December 19, 2008

Classification of cleaning enzymes…..

When ever I see a advertisement with “real enzymes” for any dish wash bar/liquids or soap powder, used to wonder what are these enzymes and how they really work and is there any difference between them (for dish washing bar and soap powders). Thanks to Guillermo et. al., who have come up with a interesting way of differentiating the types of enzymes by a method, which is based on the acid hydrolysis of the enzymes to their amino acid constituents. It is really interesting, since their first tentative introduction as minor additives in cleaning products.they have become major players. Cleaning enzymes have almost reduced the use of bleaching agents (hypochlorite solution). The advantage of these enzymes (over the bleaching agents) is better fabric care, during washing. I am sure this test will have its impact in the future, on the magical ability of the enzymes to remove so many types of marks and stains by its equally impressive way of classifying the enzymes involved.

Four types of enzymes:

1. Proteases- attack protein-rich stains such as grass and blood;

2. Amylases- remove stains that contain starch from dishes and fabrics

3. Lipases- hit fats and edible oils and

4. Cellulases- removes the fuzz balls that form on cotton

Hope this experiment will go a long way in adding more enzymes…….

Sunday, December 14, 2008

DNA strands as fibre optic cables?

DNA strands can be easily converted into tiny fibre optic cables that guide light along their length. Optical fibres made this way could be important in optical computers, which use light rather than electricity to perform calculations, or in artificial photosynthesis systems that may replace today's solar panels, claims Bo Albinsson

Though the result is similar to natural photonic wires found inside organisms like algae, where they are used to transport photons to parts of a cell where their energy can be tapped. In these wires, chromophores are lined up in chains to channel photons. It is really interesting though there are pros and cons about the claim. Hope further research in the same, will definitely substantiate the claim…..

Does individual DNA genotype, has anything to do with rapid development of AIDS?

Yes, says Stephen O'Brien and colleagues from the National Cancer Institute in Frederick. By studying the time it took for the subjects to develop AIDS-related diseases and relating it to their genetic information, the team found that some mitochondrial DNA genotypes are associated with rapid development of AIDS. For example, subjects with specific sets of variations known as U5a1 and J haplogroups progressed to AIDS at twice the average rate of the studied population. In contrast, people with the H3 haplogroup progressed more than twice as slowly.

I am sure this research could go a longway in determining, when an individual should start HIV therapy (start HAART earlier than currently recommended) and also help the doctors choose the best combination of drugs.

Source : http://www.aidsonline.com/pt/re/aids/abstract.00002030-200811300-00003.htm;jsessionid=JGPSvrMJKJ6LppdFfHJKwzpJG4HLsPDnnFnFxlgCXkPW0bp0bSVN!-595418120!181195629!8091!-1

Thursday, December 11, 2008

Nano fungus ! ....

Everything Nano…now it is the turn of fungus. German researchers, Alexander Eychm├╝ller and Karl-Heinz Peacute have discovered that they can coat the thin fronds that grow from Penicillium and other fungi with nanoscopic particles of a noble metal. They found that fungal threads coated with 200 nm gold particles appear reddish brown, as does a solution of such gold nanoparticles, providing evidence that the nanoparticulate nature of the particles is maintained during growth rather than aggregation to form larger units taking place. For more….

Tuesday, December 9, 2008

Decoding of Neanderthal genome……

Lactose intolerance, bulging brains in humans and lacking of a mutation associated with increased fertility - the answers for all these questions are being answered by microcephalna gene mutation. Neanderthal genome researchers, have half done the job and I am sure this will shed light on the evolution of modern humans after their ancestors split from Neanderthals, more than 600,000 years ago and hope they will achieve the success soon.....

Monday, December 8, 2008

Euphoria over Stem Cell Therapy.....

Now a days, I have seen many advertisements in papers, news channels and web sites regarding many clinics claiming to treat multiple diseases with the stem cells, boasting that there is no risk. And I have heard from one of my close friend, that a clinic from US claimed to treat a paraplegia patient suffering for 4 years. He spent lot of money without any result and with lots of physical and mental trauma. Its really interesting now ISSCR, (International Society for Stem Cell Research) has come to the rescue of many patients with its novel idea, by publishing the guidelines for the clinics In my opinion, the awareness should first start from medical practitioners…..

Can Antisense drugs revolutionize the drug discovery ?

Antisense therapy, is an important technology for drug discovery and development. It is broadly used by the pharmaceutical industry as a tool for functional genomics and as highly specific drugs for a wide range of diseases (Anticancer, anti-inflammatory, cardiovascular and neurodegenerative diseases) The most interesting factor of antisense drugs is “specificity” in contrast to the traditional drugs (which binds to the proteins and charge interactions so often ending with undesirable side effects). With the combined efforts of human genome programme and bioinformatics, we may soon have a lesser number of targets, I think this interesting field may revolutionize the drug discovery. But the real concern is, there are a few players as of now. In my opinion, something like High Throughput Screening (HTS), with co-ordination of educational and private institutes may help to have more drug contenders (as for as my knowledge goes, Southern Research Institute, Birmingham did try for antitubercular drugs, for the drug resistant strain). Let us hope, something happen in the near future…..