Allyl and allyloxycarbonyl groups as versatile protecting groups in nucleotide synthesis

Allyl group serves as a useful protecting group for an protection of sugar hydroxyls and amino and imide moieties of by brief treatment with a palladium catalyst and a variety of nucleophiles at room temperature.     

Kin groups and trait groups: population structure and epidemic disease selection

A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of extinction, individual selection, and migration and a population structure realistic in its general form, has implications for specific human polymorphisms such as hemoglobin variants and for the more general problem of the tempo of evolution as well.     

Blood groups of anthropoid apes and their relationship to human blood groups

Affinity between blood groups of man and those of anthropoid apes is reflected not only in similarities or identities of reactions of the red cells with many specific typing reagents, but also in overall structures of some of the main blood group systems defined in man and in apes.Besides specificities of human-type, such as A-B-O, M-N, Rh-Hr, I-i, etc. known to be present on the red cells of various species of apes, specific reagents were produced by iso- or cross-immunization of chimpanzees that detect red cell specificities characteristic for apes only. Some of those specificities were found to be shared by several ape species and to fall into separate blood group systems that are counterparts of the human blood group systems. Recently obtained serological, as well as population data, indicate that the chimpanzee R-C-E-F blood group system is the counterpart of the human Rh-Hr system. Similarly to the Rh-Hr system, it is built around a main antigen, the R^c antigen, to which secondary specificities are attached by means of multiple allelic genes. The R^c is not only the principal factor of the chimpanzee R-C-E-F group system, but also constitutes a direct link with the human Rh-Hr blood group system, since anti-R^c reagents also detect Rh₀ specificity on the human red cells. Another chimpanzee blood group system, the V-A-B-D system, is counterpart of the M-N-S-s system, and is built around the central antigen V^c. the V^c is not only the principal specificity of the chimpanzee V-A-B-D system, but it also constitutes the direct link with the human M-N-S-s system since anti-V^c reagent gives with chimpanzee red cells reactions parralleling those obtained with anti-N lectin (N^v) while in tests with human red cells it detects specificity identical or closely related to the Mi^a specificity.     

Haptoglobin groups and leukemia

Haptoglobin groups were studied in 100 leukemia patients and controls. Previously reported associations with Hp1-1 and the Hp1 gene by other investigators were not confirmed. In agreement with a previous observation a significant increase of ahaptoglobinemia (Hp0) was found among the leukemia patients.     

Oxime-phosphazenes containing dioxybiphenyl groups

2,2-Dichloro-4,4,6,6-bis[spiro(2′,2′′-dioxy-1′,1′′-biphenylyl]cyclotriphosphazene (2) was obtained from the reaction of hexachlorocyclotriphosphazene (1) with biphenyl-2,2′-diol. 2,2-Bis(4-formylphenoxy)-4,4,6,6-bis[spiro(2′,2′′-dioxy-1′,1′′-biphenylyl]cyclotriphosphazene (3) was synthesized from the reaction of 2 with 4-hydroxybenzaldehyde. The novel oxime-cyclophosphazene containing dioxybiphenyl groups (4) was synthesized from the reaction of 3 with hydroxylaminehydrochloride in pyridine. The reactions of this oxime-cyclophosphazene with propanoyl chloride, allyl bromide, acetyl chloride, methyl iodide, benzoyl chloride, 4-methoxybenzoyl chloride, benzenesulfonyl chloride, chloroacetyl chloride, ethyl bromide, benzyl chloride and 2-chlorobenzoyl chloride were studied. Disubstituted compounds were obtained from the reactions of 4 with propanoyl chloride, allyl bromide, acetyl chloride, methyl iodide, benzoyl chloride, 4-methoxybenzoyl chloride, chloroacetyl chloride, ethyl bromide, and 2-chlorobenzoyl chloride, however, the oxime groups on 4 rearranged to nitrile (11) in the reaction of 4 with benzenesulfonyl chloride. A monosubstituted compound was obtained from the reaction of 4 with benzyl chloride. All products were generally obtained in high yields. The structures of the compounds were defined by elemental analysis, IR, ¹H, ¹³C and ³¹P NMR spectroscopy.     

Simple alkanethiol groups for temporary blocking of sulfhydryl groups of enzymes.

New reagents for the temporary blocking of active or accessible sulfhydryl groups of enzymes have been developed. These reagents, which are either alkyl alkanethiolsulfonates or alkoxycarbonylalkyl disulfides, rapidly and quantitatively place various RS- groups on the sulfhydryls to generate mixed disulfides. In all cases native enzymes can be regenerated with either dithiothreitol or beta-mercaptoethanol. In general the temporary blocking groups also afford total protection against normally inhibitory thiol blocking agents. When RS- groups were attached to rabbit muscle creatine kinase (EC 2.7.3.2), a trend toward lower residual activities with increasing bulk was observed. Treatment of the native creatine kinase with 14CH3HgC1 led to incorporation of greater than 1 equiv of CH3Hg- group per subunit. This CH3Hg- blocked enzyme was fully active, and the blocking group afforded no protection against iodoacetamide. These results suggest that CH3Hg- and the RS- groups are modifying two different sulhydryl groups on the enzyme. When papain (EC 3.4.4.10) was treated with excess methyl methanethiolsulfonate. complete and rapid inhibition was observed, and 1 equiv of CH3S- was incorporated/mol of active enzyme. Complete protection against normally inhibitory 5,5'-dithiobis(2-nitrobenzoic acid) was afforded by the temporary blocking group. When rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) was titrated with methyl methanethiolsulfonate, two sulfhydryl groups per subunit were found to be modified, one much more rapidly than the other. If one extrapolates the initial slope of the titration curve, the inactivation of the enzyme would be complete after modification of a single cysteinyl residue per subunit.