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Peptide libraries displayed by T7 phage, which contain random cDNA fragments insets, were screened for their ability to bind to a biotinylated derivative of clarithromycin. Phage particles bound to an immobilized derivative of the antibiotic were isolated and the inserted cDNA was amplified and sequenced. A common selected peptide sequence, composed of 19 amino acids, was obtained and a synthetic peptide with this sequence was produced. Surface plasmon resonance experiments showed that the synthetic peptide immobilized on a sensor chip bound to clarithromycin and the dissociation constant was determined to be 2.1ϫ10 Ϫ3 M. The dissociation constants of other macrolide antibiotics, erythromycin, roxithromycin, azithromycin and josamycin were also determined to be 5.4ϫ10 Ϫ3 M, 6.2ϫ10 Ϫ5 M, 1.1 M and 3.4ϫ10 Ϫ2 M, respectively. These results indicated that T7 phage display method might be useful to determine relatively weak interactions between small molecule drugs and the selected peptides which could represent a possible binding site conserved in binding proteins.

Rat pancreatic islets were allografted in the liver and were studied morphologically in order to evaluate possible reinnervation. Islets isolated from rat pancreas were allotransplanted in the liver of streptozocin-induced diabetic rats via the portal vein. Electron microscopy revealed nerve endings with synaptic vesicles in the transplanted islets 100 days after transplantation, whereas axons in the islets appeared to degenerate several hours after isolation and prior to transplantation. These findings suggest that the nerve endings observed in the transplanted islets regenerate from nerves that innervate the recipient's liver. The tissue specimens were also investigated immunohistochemically using antityrosine hydroxylase antibody, and histochemically by the modified Karnovsky and Roots' method for visualizing acetylcholinesterase. Some nerve endings in the transplanted islets reacted positively to antityrosine hydroxylase antibody. Acetylcholinesterase was visualized in other nerves. These results indicate that norepinephrine- and acetylcholinesterase-containing nerves may reinnervate the transplanted islets.

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