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Novel cobalt bis(dicarbollide) terminal alkynes with charge-compensated group were synthesized by the cleavage reactions of oxonium derivatives of cobalt bis(dicarbollide) with N,N-dimethylprop-2-yn-1-amine. The solid-state molecular structures of alkynes prepared from 1,4-dioxane and tetrahydropyran derivatives of cobalt and iron bis(dicarbollide) were determined by single-crystal X-ray diffraction. A series of zwitterionic conjugates of cobalt/iron bis(dicarbollide) with cholesterol were prepared using the copper(I)-catalyzed azide-alkyne cycloaddition reaction. [ABSTRACT FROM AUTHOR]

Recent studies have implicated a role of the epidermal growth factor receptor (EGFR) pathway in kidney disease. Skin toxicity associated with therapeutics which completely block the EGFR pathway precludes their use in chronic dosing. Therefore, we developed antibodies which specifically neutralize the EGFR ligands TGFα (transforming growth factor-alpha) and epiregulin but not EGF (epidermal growth factor), amphiregulin, betacellulin, HB-EGF (heparin-binding epidermal growth factor), or epigen. The epitope of one such neutralizing antibody, LY3016859, was characterized in detail to elucidate the structural basis for ligand specificity. Here we report a crystal structure of the LY3016859 Fab fragment in complex with soluble human TGFα. Our data demonstrate a conformational epitope located primarily within the C-terminal subdomain of the ligand. In addition, point mutagenesis experiments were used to highlight specific amino acids which are critical for both antigen binding and neutralization, most notably Ala41, Glu44, and His45. These results illustrate the structural basis for the ligand specificity/selectivity of LY3016859 and could also provide insight into further engineering to alter specificity and/or affinity of LY3016859. [ABSTRACT FROM AUTHOR]

The association between alcoholism and the Taql "A" and "B" polymorphic alleles at the DRD2 gene and 48-bp tandem repeat in exon 3 of dopamine D4 recepwr (DRD4) gene in 42 unrelated Slavic-surnamed patients and 76 normal controls was examined. The frequency of the A1 allele was higher in alcoholic patients and in alcoholic patients with a family history of alcoholism than in controls (Chi[sup 2] = 3.45, p < O. 001 and Chi[sup 2] = 3. 97, p < 0. 001, respectively). Moreover, the frequency of the A1 allele was higher in alcoholics with a family history of alcoholism than in alcoholics without a family history (Chi[sup 2] = 3.33, p < O. 001). The results of association analysis for both the Taql "B" and DRD4 alleles were negative for alcoholics in general, subgroups of alcoholics and normal controls. However, the 7-repeat allele (DRD4*7R) of DRD4 gene occurred at significantly higher frequency in alcoholics with a family history of alcoholism compared with those without a family history (Chi[sup 2] = 3.42, p < 0.01). The results indicate that the A1 allele of the DRD2 gene is associated with susceptibility to alcoholism in general The A1 allele, as well as the DRD4*7R allele, is significantly prevalent among alcoholics with a family history, in comparison with alcoholics without a family history, reflecting different roles of genetic factors in development of alcoholism. [ABSTRACT FROM AUTHOR]