Synthesis of N-carboxyalkyl and N-aminoalkyl functionalized dipeptide building units for the assembly of backbone cyclic peptides.

To improve the assembly of backbone cyclic peptides, N-functionalized dipeptide building units were synthesized. The corresponding N-aminoalkyl or N-carboxyalkyl amino acids were formed by alkylation or reductive alkylation of amino acid benzyl or tert-butyl esters. In the case of N-aminoalkyl amino acid derivatives the aldehydes for reductive alkylation were obtained from N,O-dimethyl hydroxamates of N-protected amino acids by reduction with LiAlH4. N-carboxymethyl amino acids were synthesized by alkylation using bromoacetic acid ester and the N-carboxyethyl amino acids via reductive alkylation using aldehydes derived from formyl Meldrums acid. Removal of the carboxy protecting group leads to free N-alkyl amino acids of very low solubility in organic solvents, allowing efficient purification by extraction of the crude product. These N-alkyl amino acids were converted to their tetramethylsilane-esters by silylation with N,O-bis-(trimethylsilyl)acetamide and could thus be used for the coupling with Fmoc-protected amino acid chlorides or fluorides. To avoid racemization the tert-butyl esters of N-alkyl amino acids were coupled with the Fmoc-amino acid halides in the presence of the weak base collidine. Both the N-aminoalkyl and N-carboxyalkyl functionalized dipeptide building units could be obtained in good yield and purity. For peptide assembly on the solid support, the allyl type protection of the branching moiety turned out to be most suitable. The Fmoc-protected N-functionalized dipeptide units can be used like any amino acid derivative under the standard conditions for Fmoc-solid phase synthesis.     

An Ecological Imbalance Induced by a Non-Native Species: The Manila Clam in the Venice Lagoon

Among the 19 non-native species of marine invertebrates which have invaded the Venice Lagoon and have established populations, Ruditapes philippinarum, deliberately introduced in 1983, is surely the most successful species. According to the hypothesis that alien species invasion could be favoured by an altered ecological, chemical or physical state of the system induced by anthropogenic disturbance, R. philippinarum turned out to be ‘the right species at the right moment’. By comparing historical data (1968, 1985, 1990) with 1999 data, changes in macrobenthic community, in particular bivalve molluscs, of the lagoon induced by R. philippinarum introduction and subsequent clam exploiting activity were assessed. It has been possible to describe a sharp reduction, both in terms of distribution area and density, of all other filter feeder bivalves. Moreover, by using the clearance rate of the most abundant bivalve species in 1990 and 1999 (Cerastoderma glaucum and R. philippinarum, respectively), it was possible to estimate that the filtration capacity, expressed as l h⁻¹ m⁻², has more than doubled. This has altered the functioning of the ecosystem, resulting in a stronger benthic–pelagic coupling. In this context, R. philippinarum attains control of the system. Considering all this, it is possible to state that the Venice Lagoon ecosystem has entered into a new state, probably more resistant but less resilient, with implications for future management choices.     

Characteristics of interhemispheric relationships in the absence or presence of a skill

A comparative analysis of the time and amplitude characteristics of the negative N200 and positive P300 components of visual evoked potentials recorded at symmetric points of the frontal, parietal, temporal, and occipital areas of the right and left hemispheres of the cerebral cortex has been performed in subjects with or without the skill of operating a computer. Subjects inexperienced in an operator’s work exhibited an interhemispheric difference in the time and amplitude characteristics of the studied components. In subjects that had the skill of operating a computer, the interhemispheric difference was little, which suggests that the cortex plays only a small role in the cerebral control of this activity.     

INTERVENTION OF BRAIN CORTEX PHOSPHOLIPIDS IN PYRIDOXAL PHOSPHATE-DEPENDENT REACTIONS

We have examined the role of brain cortex phospholipids in regulating some enzymic reactions specific to the CNS. The study was carried out at the level of the reactions concerned with GABA formation, both in vivo and in vitro, and included investigation of the specificity of the effect. It was found that the brain cortex phospholipids enhance the transformation of exogenous vitamin B₆ into pyridoxal-5-phosphate by activating the pyridoxal 5-phosphate-kinase enzyme, in contrast to other phospholipids of different origins. The possible role of brain cortex phospholipids in regulating an enzyme contained in the soluble fraction is discussed. Moreover, it is suggested that the specific effect of the phospholipids from various sources is linked to their fatty acid composition and to be therefore dependent on the aliphatic chains.