Racemic diastereoisomers of 1-amino-2-hydroxycyclopentanecarboxylic acid.

The synthesis and characterization of the two diastereoisomeric forms of 1-amino-2-hydroxycyclopentanecarboxylic acid have been accomplished. A previously reported synthesis produced a racemic mixture of the threonine analog trans-2-hydroxy-1-aminocyclopentanecarboxylic acid (trans with respect to the hydroxy and carboxyl group). The alternate allothreonine analog was produced by conversion of cyclopentene oxide to trans-2-methoxycyclopentanol, followed by oxidation to 2-methoxycyclopentanone and conversion to a hydantoin. Fractional crystallization of the hydantoin sample, followed by hydrolysis, produced cis-2-hydroxy-1-aminocyclopentanecarboxylic acid (cis with respect to the hydroxy and carboxyl group) in high purity. Neither of the isomeric forms significantly inhibited the growth of the bacterial strains examined nor were they effective in inhibiting Jensen sarcoma cells in tissue culture.

Synthesis and biological activity of 8-oxadihydropteridines.

A series of 6-substituted and 6,7-disubstituted pyrimido[4,5-b][1,4]oxazines (8-oxadihydropteridines) was synthesized through the condensation of an alpha-halo ketone and 2,5-diamino-4,6-pyrimidinediol. The resulting 8-oxadihydropteridines were assayed as potential antifolates in a dihydrofolate reductase enzyme system. The 2-amino-4-hydroxyoxa-dihydropteridines were found to possess greater biological activity than the corresponding 2,4-diamino compounds. The pteroic acid homeostere 2-amino-4-hydroxy-6-phenethyl-8-oxadihydropteridine was the most potent of the compounds tested.

The gamma-globin genes and their flanking sequences in primates: findings with nucleotide sequences of capuchin monkey and tarsier.

By sequencing extensive regions of the beta-globin gene cluster from capuchin monkey (New World monkey) and tarsier (prosimian) we confirmed that capuchin monkey and tarsier have two and one gamma-globin gene(s), respectively. These findings indicate that the ancestral anthropoid gamma-globin gene duplicated after anthropoids diverged from tarsier, but before they diverged into platyrrhines (New World monkeys) and catarrhines (Old World monkeys, apes, and human). The capuchin monkey gamma 1-globin gene promoter region accumulated many nucleotide substitutions, including a T to C substitution in the proximal CCAAT element. This adverse mutation, along with the previous finding that the gamma 1 locus in spider monkey is a pseudogene, suggests that in platyrrhines the gamma 2-globin gene may be the primary fetal beta-like globin gene. The aligned gamma gene sequences contain several conserved sequence elements (phylogenetic footprint) of 6 bp or longer in the 5' flanking region, but none in the 3' flanking region. Gene conversions frequently occurred in the 5' flanking and transcribed regions of the duplicated genes of anthropoids but rarely in the 3' flanking sequences. However, an absence of conversions within the capuchin and spider monkeys promoter regions suggests that in platyrrhines selection acted against conversions as they could decrease (or inactivate) gamma 2 expression.

Inhibitory Effects of Dichlorophenoxyacetones on Auxin-induced Growth of Avena Coleoptile Sections.

Six dichlorophenoxyacetones were synthesized and examined as potential metabolic antagonists utilizing Avena coleoptile sections and the straight growth assay procedure. Supplements of indoleacetic acid promoted growth of the sections which were inhibited by the analogs; the most inhibitory derivatives were 2,3-; 2,4-; 2,5-; and 3,4-dichlorophenoxyacetone which produced half-maximal growth responses (relative to the unaug-mented control growth) at concentrations of 106, 86, 80, and 62 mug/ml, respectively. A Lineweaver-Burk plot of the data for the inhibition by 2,4-dichlorophenoxyacetone and its reversal by indoleacetic acid appeared to represent an uncompetitive-like inhibition.

Antimetabolites of pantothenic acid, ureido- and carbamoyl-derivatives.

Pantothenic acid analogs have been synthesized that contain alkyl and/or arylureido and carbamate functions in the beta-alanyl portion of the amide moiety of the vitamin. The analogs are inhibitory to growth of lactic acid bacteria at concentrations as low as 0.6 mug/ml, and the inhibitions are competitively reversed by supplements of pantothenic acid. The carbamate derivatives are more toxic to growth of Lactobacillus plantarum 8014 and Pediococcus cerevisiae 8042 than the ureido analogs, and chloro-substitutents on the aryl group significantly increase the toxicity of the analogs.

Reexamination of the African hominoid trichotomy with additional sequences from the primate beta-globin gene cluster.

Additional DNA sequence information from a range of primates, including 13.7 kb from pygmy chimpanzee (Pan paniscus), was added to data sets of beta-globin gene cluster sequence alignments that span the gamma 1, gamma 2, and psi eta loci and their flanking and intergenic regions. This enlarged body of data was used to address the issue of whether the ancestral separations of gorilla, chimpanzee, and human lineages resulted from only one trichotomous branching or from two dichotomous branching events. The degree of divergence, corrected for superimposed substitutions, seen in the beta-globin gene cluster between human alleles is about a third to a half that observed between two species of chimpanzee and about a fourth that between human and chimpanzee. The divergence either between chimpanzee and gorilla or between human and gorilla is slightly greater than that between human and chimpanzee, suggesting that the ancestral separations resulted from two closely spaced dichotomous branchings. Maximum parsimony analysis further strengthened the evidence that humans and chimpanzees share the longest common ancestry. Support for this human-chimpanzee clade is statistically significant at P = 0.002 over a human-gorilla clade or a chimpanzee-gorilla clade. An analysis of expected and observed homoplasy revealed that the number of sequence changes uniquely shared by human and chimpanzee lineages is too large to be attributed to homoplasy. Molecular clock calculations that accommodated lineage variations in rates of molecular evolution yielded hominoid branching times that ranged from 17-19 million years ago (MYA) for the separation of gibbon from the other hominoids to 5-7 MYA for the separation of chimpanzees from humans. Based on the relatively late dates and mounting corroborative evidence from unlinked nuclear genes and mitochondrial DNA for the close sister grouping of humans and chimpanzees, a cladistic classification would place all apes and humans in the same family. Within this family, gibbons would be placed in one subfamily and all other extant hominoids in another subfamily. The later subfamily would be divided into a tribe for orangutans and another tribe for gorillas, chimpanzees, and humans. Finally, gorillas would be placed in one subtribe with chimpanzees and humans in another, although this last division is not as strongly supported as the other divisions.