N C O'Neill | PubMed Health

PubMed1991

Structure-activity studies of vasoactive intestinal polypeptide.

This report explores the potential side-chain functional groups required for interaction of the bronchodilator neuropeptide, vasoactive intestinal peptide (VIP), with its receptor. The binding affinity and biological activity of native VIP have been found to be sensitive to the removal of amino- and carboxyl-terminal residues. This data suggests that elements within the entire primary sequence of the VIP molecule appear to be necessary for recognition by VIP receptors. The introduction of alanine residues substituted into the VIP molecule is utilized to probe for side-chain functional groups that are crucial for eliciting high receptor binding affinity in vitro and high biological potency in vivo. The VIP pharmacophore appears to be identical in guinea pig lung and human lung and consists of multiple binding sites most likely involving positions Asp3, Phe6, Thr7, Tyr10, Tyr22, and Leu23. These findings could be exploited to enhance the biological potency of VIP by increasing the binding energy at these positions.

Alanine↗

PubMed1989

Uptake of copper from brass vessels by bovine milk and its relevance to Indian childhood cirrhosis.

To mimic the infant feeding practice associated with Indian childhood cirrhosis (ICC), bovine milk was stored for 6 h in indigenous brass vessels. The milk copper concentration rose from 27 +/- 4 to 621 +/- 65 micrograms/dl, whereas zinc concentration was not significantly changed. Copper in bovine milk was associated with casein (67%), whey proteins (7%), less than 10 kDa molecules (11%), and fat (7%). Addition of copper sulphate to a concentration of 600 micrograms/dl produced a 102-fold rise in copper content of the casein fraction, a 47-fold increase for whey, and 15-fold for the less than 10 kDa fraction. Analysis by sepharose gel chromatography confirmed that casein was the major copper-binding fraction in control and copper-loaded milk. To mimic intragastric conditions, the pH of copper-loaded milk was lowered to 4.5 to precipitate casein, resulting in a rise in less than 10 kDa bound copper (10.7 +/- 4.0 to 104.3 +/- 7.5 micrograms Cu/100 ml) and whey-bound copper (53.1 +/- 4.5 to 118.4 +/- 19.1 micrograms Cu/100 ml). Copper/casein complex (3 micrograms Cu/mg protein, pH 6.6) was dialysed against low-MW metal chelating agents, including picolinate and citrate, which are present in the duodenum. Picolinate 1 mM and citrate 1 mM were able to remove 84% and 29% of copper, respectively. Thus, copper, though not zinc, is avidly taken up from brass and bound largely to casein, from which it is partly liberated by acid precipitation and almost completely removed by picolinate chelation. Milk is an effective carrier of copper from brass utensil to infant enterocyte.

Animals↗