Interaction of VO ion with human serum transferrin and albumin

The complexation of VO²⁺ ion with the high molecular mass components of the blood serum, human serum transferrin (hTf) and albumin (HSA), has been re-examined using EPR spectroscopy. In the case of transferrin, the results confirm those previously obtained, showing that VO²⁺ ion occupies three different binding sites, A, B₁ and B₂, distinguishable in the X-band anisotropic spectrum recorded in D₂O. With albumin the results show that a dinuclear complex (VO)₂^dHSA is formed in equimolar aqueous solutions or with an excess of protein; in the presence of an excess of VO²⁺, the multinuclear complex (VO)_x^mHSA is the prevalent species, where x = 5-6 indicates the equivalents of metal ion coordinated by HSA. The structure of the dinuclear species is discussed and the donor atoms involved in the metal coordination are proposed on the basis of the measured EPR parameters. Two different binding modes of albumin can be distinguished varying the pH, with only one species being present at the physiological value. The results show that the previously named “strong” site is not the N-terminal copper binding site, and some hypothesis on the metal coordination is discussed, with the ⁵¹V A_z values for the proposed donor sets obtained by DFT (density functional theory) calculations. Finally, preliminary results obtained in the ternary system VO²⁺/hTf/HSA are shown in order to determine the different binding strength of the two proteins. Due to the low VO²⁺ concentration used, the recording of the EPR spectra through the repeated acquisition of the weak signals is essential to obtain a good signal to noise ratio in these systems.     

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors.     

Update on the presence of taste buds on the laryngeal surface of the epiglottis]

Previous investigations have ascertained, according to the results obtained by Bradley et al. (1980) in the sheep, that the laryngeal surface of the epiglottis of goat and bovine is always provided with numerous taste buds. These observations have verified in other ruminant species, as the moufflon and the buffalo, the validity of the above-named datum and have ascertained that it is always inconstant in the other animal species considered (wild boar, coypu). These taste buds show a typical structure (diameter of the outer taste pore varying from 2.7 to 4.2 micron, width of the chemoreceptors varying from 30 to 60 micron and length from 27.5 to 57.5 micron). Moreover, the normal structure of the above-named taste buds is also testified by the arrangement of their innervation and particularly by the integrity of the synaptic contacts. The results of the present research have permitted a critical and more severe examination of the probable functional role of those laryngeal receptors. In fact, in the ruminants they may protect the deep airways precluding to food particles the larynx in the phase of food regurgitation.