DNA binding, solubility, and partitioning characteristics of extended lexitropsins.

Four new ligands that bind to the minor groove of DNA have been designed, synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides containing central regions with five or six N-methylpyrrole units, conferring hydrophobicity and good binding affinity but without retaining the correct spacing for hydrogen bonding in the base of the minor groove. The two remaining ligands have central regions which are head-to-head-linked polyamides, in which the linker is designed to improve the phasing of hydrogen bonding of the ligand with the floor of the minor groove. The highest affinity was obtained with the two polypyrroles without headgroup spacers, indicating that H-bond phasing is secondary in determining affinity compared to the major hydrophobic driving force. With a dimethylaminoalkyl group, representing a moiety with modest base strength, at both ends, water solubility is good and pH-partition theory predicts that penetration through lipid membranes will be enhanced, compared to strongly basic amidine analogues of the alkaloid precursors. All four compounds bind to DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs and subtle individual preferences. The data show that very high affinities can be anticipated for future compounds in this series, but drug design must take account of overall physicochemical properties as well as the details of hydrogen bonding between ligands and the floor of the minor groove.

3-Acetoxycyclohex-4-ene-1,2-dicarboxylic anhydride.

The title compound, C(10)H(10)O(5), was found to exist as the endo-cis isomer with a pair of enantiomers in the asymmetric unit. The cyclohexene ring is folded about the methylene-to-CH(acetoxy) vector to give a boat conformation.

Technetium-99m-MIBI myocardial SPECT: supine versus right lateral imaging and comparison with coronary arteriography.

UNLABELLED: Myocardial perfusion SPECT using the prone position improves inferior wall counts and decreases motion problems as compared with the usual supine position. Nonetheless, it is not suitable for women. In addition, it is associated with artifactual anteroseptal defects and hot spots. METHODS: The right lateral (RL) position was evaluated instead of the prone position in 72 patients (26 women). RL imaging was performed immediately after the supine imaging during a routine 2-day 99mTc-sestamibi exercise protocol. The SPECT images were scored semiquantitatively by three physicians. Moreover, regional myocardial counts, as well as extent and severity of defects, were assessed by quantitative polar map analysis. RESULTS: All patients tolerated the RL position well and there was no significant patient movement in either position. Higher inferior myocardial counts per pixel were observed in the RL than in supine images. Inferior wall defects (especially mild ones) were more common in the supine than the RL images, whereas defects in other regions were not different. Quantitative analysis confirmed these findings. Analysis of 34 patients with recent coronary arteriography revealed an overall coronary artery disease (CAD) supine- and RL-imaging specificity of 50% and 75%, respectively, and the sensitivities of both were 93%. Right CAD sensitivity, specificity and normalcy rates for the supine position were 100%, 44% and 55%, whereas those of the RL position were 94%, 75% and 90%, respectively. CONCLUSION: The RL position improves CAD diagnostic accuracy, particularly right CAD, without significant artifacts in other myocardial regions. Unlike the prone position, the RL position is well tolerated by both women and men.

Catalytic antibodies: a new window on protein chemistry.

Catalytic antibodies have created a new dimension in protein chemistry. In these studies it is particularly valuable to investigate systems for which natural enzymic catalysts are unknown. At Strathclyde we have examined several ways of preparing homochiral building blocks for organic synthesis. Antibodies that catalyse the Diels-Alder reaction have been characterized. The target reaction was the addition of acetoxybutadiene to N-substituted maleimides, a reaction that should give a pentafunctional homochiral building block. Catalytic antibodies can give insight into the mechanism of catalysis by proteins. We have investigated an adventitious hydrolytic antibody that cleaves activated esters. We have also shown that an antibody raised to ampicillin for analytical purposes catalyses hydrolysis of the beta-lactam ring.