Saturday, March 15, 2008

Why are we made of only left-handed amino acids? A molecular concept of Life.

Most biomolecules are "chiral", that is to say, they exist in two left and right-handed mirror-image forms. However, biology only uses one hand, i.e., it is "homochiral". Life on Earth is made of left-handed amino acids, almost exclusively. One of the greatest puzzles in biophysics is the question of why life on Earth is based on left-handed (L) amino acids? Moreover, the synthesis of single enantiomers (ee ~100%) is one of the most critical industry demands.

Recently Prof. Pedro Cintas described that fractional sublimation of chiral organic compounds improves ee substantially.

The reported results provide a beneficial protocol for the resolution of racemates. Additionally, it suggests that improvement of optical activity by such a thermal process could be more efficient than or at least an alternative to spontaneous crystallization of suitable compounds.

He conclude that sublimation should be regarded as a reasonable mechanism for the formation of optically active crystals in the prebiotic world. Subsequent stochastic sorting of crystals of enantiopure compounds by natural agents might have generated highly enantiopure niches, which might be responsible for the prevalence of homochirality in nature.

Molecular evolution might lead to life, but it is not scientifically valid because life is a non-physical, non-chemical entity.

Saturday, March 8, 2008

The Histamine H4 Receptor: Drug Discovery in the Post-genomic Era

The Histamine H4R receptor is the most recently identified G-protein coupled receptor, with little homology to the classical pro-inflammatory histamine H1 or the histamine H2 receptor, and some 35% homology with H3 receptor.



 The high expression of the histamine H4 receptor in cells of hemopoietic lineage and immune cells suggests that this new histamine receptor plays a role in inflammatory and immune responses. Activation of the Histamine receptor can mediate calcium mobilization and chemotaxis in mast cells.

Preliminary studies on the H4R and specific antagonist (JNJ 7777120 - Johnson & Johnson, VUF6002-Janssen Pharma.) suggest another rich vein of histamine receptors therapeutics, likely to generate more blockbusters and medical breakthroughs, could be on the horizon.

Ref: Nature Reviews Drug Discovery, 7, 41-53, 2008, Trends Pharmacol. Sci. 26, 462-469, 2005.