Synthesis of a new carrier for immunization: polytuftsin. Two examples of its use with peptides selected in the hepatitis B surface antigen

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCl)-Thr-Lys-(2-Cl-Z)-Pro in the presence of HOBt. Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10-26 and 39-55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA. Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCl 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

Selective emergence and survival of early polypeptides in water

Oligopeptides essential to primitive cells could not be obtained just by raising the background noise of organic compounds produced by a prebiotic chemistry working at random. Selection pathways were required. Experimental evidence is given for selective condensation of amino acids in water as well as for selective resistance to degradation. It is shown that N-carboxyanhydrides are good candidates for chemical selection in water. They are formed when active esters of amino acids are left in the presence of bicarbonate ions or when N,N'-carbonyldiimidazole is used as condensing agent. Polymerization of a mixture of proteinaceous and non-proteinaceous amino acids leads to an enrichment in the proteinaceous ones plusα-aminobutyric acid. Selective resistance toward degradation ofβ-pleated sheet conformation is used to exemplify a possible accumulation of homochiral sequences made of hydrophilic and strong hydrophobic residues. Amino acids with branched aliphatic side-chains are selected but those having short linear aliphatic side-chains such asα-aminobutyric acid or norvaline are not.     

Solid-state conformation of some basic sequential polypeptides

We have studied the structure of solid films obtained by x-ray diffraction, from several basic polypeptides with a defined sequence. The alterating polypeptides poly(Ala-Lys), poly(Leu-Lys), poly(Val-Lys), and poly(Arg-Leu) all show a cross-β-structure in which layers of hydrophilic side chains alternate with layers containing hydrophobic side chains. The other polypeptides studied are not in the β-conformation and appear to be in the α-helical conformation. The helices obtained from poly(Lys-Ala-Ala) and poly(Lys-Ala-Ala-Lys) appear to be packed in an unusual fashion, which favors interaction between alanine side chains. Such behavior is not found in poly(Lys-Leu-Ala).     

Renal papillary adenoma in a cotton-topped tamarin (Saguinus oedipus)

The second case of a renal tumour in a tamarin is described. The incidentally discovered unilateral tumour developed in an adult female cotton-topped tamarin. It did not cause clinical symptoms and was classified as a papillary adenoma based on its morphological characteristics.     

The phylogeny of the hominoid primates: a statistical analysis of the DNA-DNA hybridization data

Sibley and Ahlquist compared the single-copy nuclear DNA sequences of the hominoid primates using DNA-DNA hybridization. From this data set they estimated a phylogeny that clusters man and chimpanzees using a distance Wagner procedure. However, no assessment of statistical confidence in this estimated phylogeny was made, despite the fact that their data set contains internal inconsistencies concerning the correct branching order. This paper presents a modification of Pielou's Q- statistic that allows one to make nonparametric tests of phylogenetic relationship from distance data. The results of this analysis indicate that the estimated phylogeny of Sibley and Ahlquist is without statistical significance owing to the internal inconsistencies of the data set. A survey and additional analyses of other types of molecular data indicate that the phylogeny that clusters chimpanzees and gorillas and has the human lineage splitting off earlier is statistically consistent with all the molecular data (including the DNA-DNA hybridization data), whereas the phylogeny estimated by Sibley and Ahlquist can be rejected at the 5% level using the data on restriction- endonuclease sites in the mitochondrial genome.      

Interactions ofCandida albicans with bacteria and salivary molecules in oral biofilms

The yeastCandida albicans coaggregates with a variety of streptococcal species, an interaction that may promote oral colonization by yeast cells.C. albicans andCandida tropicalis are the yeasts most frequently isolated from the human oral cavity and our data demonstrate that both these species bind toStreptococcus gordonii NCTC 7869 while two otherCandida species (Candida krusei andCandida kefyr) do not. Adherence ofC. albicans was greatest when the yeast had been grown at 30° C to mid-exponential growth phase. For 21 strains ofC. albicans there was a positive correlation between the ability to adhere toS. gordonii and adherence to experimental salivary pellicle. Whole saliva either stimulated or slightly inhibited adherence ofC. albicans toS. gordonii depending on the streptococcal growth conditions. The results suggest that the major salivary adhesins and coaggregation adhesins ofC. albicans are co-expressed.     

Liquid water and the origin of life

Liquid water has many peculiarities which confer special properties. The most important among them probably are the ability to establish hydrogen bonds, a high polarity and a high dielectric constant. In the presence of liquid water, large organic molecules have to manage the conflict between hydrophobic groups and hydrophilic groups. This duality can generate interesting prebiotic situations such as the stereoselective aggregation of short peptide sequences of alternating hydrophobic — hydrophilic residues into thermostable -sheets endowed with chemical acrivity. Liquid water is also a powerful hydrolytic agent. As such, it allows pathways which would have few chances to occur in an organic solvent.Presented at the Session Water in the Solar System and Its Role in Exobiology during the 26th General Assembly of the European Geophysical Society, 22–26 April 1991 in Wiesbaden, Germany.     

Synthesis of RNA I by the RNA polymerase from Micrococcus luteus on the Escherichia coli plasmid pBR322

A mutant strain of Bacillus megaterium, arising spontaneously and resistant to micrococcin , possesses ribosomes which contain an altered form of protein BM-L11 (the homologue of Escherichia coli protein L11). Reconstitution analysis has revealed that the alteration to protein BM-L11 is the sole cause of resistance in this strain.     

Synthesis and beta-conformation of copolypeptides with alternating hydrophilic and hydrophobic residues

Copolypeptides with alternating hydrophilic and hydrophobic residues were prepared, and their ability to form beta-structures in aqueous solutions was investigated by circular dichroism. Optically pure samples of poly (Lys-Leu-Lys-Leu) and poly (Leu-Glu-Leu-Glu), obtained via the 2-hydroxyphenyl esters, undergo a coil-to-beta transition in presence of salt. The beta-structures obtained under identical conditions with partially racemized samples of poly (Leu-Lys)Np and poly (Leu-Glu)Np, prepared by polycondensation of the corresponding dipeptide p-nitrophenyl esters, appear to be less regular. Non-alternating poly (Gly-Lys-Leu-Lys-Leu) does not form beta-structures in presence of NaCl as does alternating poly (Lys-Leu-Lys-Leu) indicating that the amino acid sequence can dramatically change the tendency to form beta-structures.