Modelling BBB

I was disussing about molecular shuttles/ cargos to transport potent theraputic agents across BBB.
Here a recent paper i saw in Nature Rev. Drug Discov. 6, 650, 2007. It is an extensive review regarding various In vivo and in vitro methods to study and assess BBB function. Very good review on the modelling of in vitro BBB a simplification of in vivo situation. Modelling of BBB have several advantages among that the most important is for making early perdections about the brain uptake of the potential drug candidate and to study the effect of therapeutic interventions at the level of cerebral capillaries.
These kind of models also access the risk of taking the molecules further into the clinical study, as many promising drug candidates fail to pass BBB. So these models can be preformed at the industry level before spending money and effort on potential drug candidate to take it further.
A well charaterised in vitro BBB cell model can also provide a valuable tool for studying the mechanestic aspects of transport as well as biological process.

So in the coming weeks i hope i will post more citations in the area of BBB, CNS, Neurochemistry and Neurodegenarative diseases.

It is a long weekend in sydney. Have a nice time.
Ahamed.

DNA - Templated Aldol Reaction

Hi all,
A recent paper (Angew. Chem. Int. Ed. 2007, 46, 7297-7300.) which i found intersting was based on DNA- templated reactions. There are only two reports on DNA - templated reactions thus far.

In this paper a Proline tethered to a DNA strand can efficiently catalyzed the cross aldol reaction of a complementary DNA - Aldehyde conjugate with a non - tethered ketone. The intresting aspect was the catalytic turnover achieved first time in a DNA templated reaction.

Good paper to read on.

Ahamed.

Blood Brain Barrier

A recent paper i seen on JACS worth reading to know about some concepts in Chemistry-Biology interface. When i was working on a Nuerodegenarative diseases in Banglore for a Drug Discovery frim, we faced a potential problem exactly which is discussed in this current papper.
We had sucessfully screened a potent molecule for that diseases, but the problem of Blood Brain Barrier(BBB). It was indeed a large molecule with molecular weight > 400, it showed active resistance to pass the BBB. So finally 4 years work went into the rubbish bin.
Around 98% of the small molecules and 100% of the large molecules fail to became a drug because of their in ability to pass through BBB. The prescence of the HIV in the CNS and Cerebral fluid is the prime cause for no theraphy yet for AIDS, as the potent drugs fail to pass the BBB.

So bascically in this paper they have synthezised some BBB-Shuttles, which acts as cargo for the potent molecules to penetrate in the the brain.

The passive diffusion has been studied through (i) Parallel Artificial Membrane permeability Assay (PAMPA) and (ii) Immobalized Artificial Membrane Chromatography (IAMC).

A nice paper to read on. See the paper from more detailed information.

JACS, 2007, 129, 11802-11813.

Ahamed.

Molecule-- This is a test post

This is a test post on carbon&hydrogen.

MHT Research Group

Dr.Mathew.H.Todd, Department of chemistry,University of Sydney.

Welcome to Carbon&Hydrogen

Dear all,
This is a new blog dedicated for synthetic organic chemistry & medicinal chemistry. I hope there will be few intresting posts very soon.