Biomedical subjects

A E Koziol

Publications and source records attributed to A E Koziol.

2 recordsLinked to original sources

PubMed1997

Conformational flexibility of serotonin1A receptor ligands from crystallographic data. Updated model of the receptor pharmacophore.

Preparation and affinity to 5-HT1A and 5-HT2A receptors of new buspirone analogues 7-17 are reported. The compounds possess high to low affinity to 5-HT1A and moderate to low to 5-HT2A receptors. The crystal structures have been determined for compounds 11, 12, 13, and 14. For low affinity ligand (15) of 5-HT1A receptor conformational analysis was performed and compared with similar analyses performed for know high (buspirone 1) and very high (WY-48,723 2) affinity ligands of the receptor. Structure-activity relationship is discussed for the affinity to 5-HT1A receptor. A three-point pharmacophore explaining interactions of buspirone-like molecules with the receptor binding site is proposed.

Animals↗

PubMed1988

A non-classical intercalation model for a bleomycin amplifier.

The bleomycin amplifier 1 is sterically hindered and twisted about the torsional bond joining the two aromatic rings. The intercalation of 1 and its sterically unhindered isomer 2 with DNA has been studied using n.m.r., viscometric titrations of superhelical and linear DNA, and flow dichroism. Based on the unusually strong interaction of 1 with DNA base pairs, a non-classical intercalation model for this compound is proposed. The intrinsic twists of both the unfused biaromatic system of 1 and the hydrogen-bonded DNA base pairs are retained in the intercalator-DNA complex, and the methyl group of 1 is accommodated between the hydrogen bonded bases. The complex of 1 is the first example found to date of this type of intercalation of the methyl group with DNA. The structure-activity relationships as bleomycin amplifiers for 1, 2 and similar derivatives is discussed.

Bleomycin↗