The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Molecular structures of 2,4-diaminopyrimidine antifolates with antineoplastic activity.

2,4-Diamino-5-(1-adamantyl)-6-methylpyrimidine (DAMP) and its ethanesulfonate salt (DAMP-ES) are potent inhibitors of mammalian dihydrofolate reductase and also inhibit the growth of cultured cells as effectively as the drug methotrexate (MTX). DAMP is currently in phase I clinical studies. An analogue of DAMP having 5-(1-naphthyl) in place of the adamantyl group ( DNMP) possesses little cytotoxic as well as enzyme inhibitory activity. The crystal and molecular structures of DAMPM-ES and DNMP were determined in order to elucidate the conformational aspects of drug specificity. The molecular conformation of DAMP-ES shows that the C8--C7 bond of the adamantyl ring is nearly coplanar with the pyrimidine ring (C8--C7--C5--C6 = 7.5 degrees) instead of staggered as expected from steric considerations. As a result, the pyrimidine ring and its 4,6-substituents are severely distorted from coplanarity. In DNMP, the 1-naphthalene ring is perpendicular to the pyrimidine ring (C8--C7--C5--C6 = -87.0 degrees) which is itself planar. N1 is protonated in DAMP-ES but not in DNMP. When the two structures are compared, the 5-substituents occupy different regions of space, with the outer ring of the naphthalene group outside of the volume occupied by the adamantyl ring. Therefore, the reduced effectiveness of DNMP may be caused by the inability of the naphthalene to fit the binding site in dihydrofolate reductase. This is the situation when DNMP is placed in the methotrexate binding site of Lactobacillus casei crystal structure.[1]

References

 
WikiGenes - Universities