The aim of this study was to design and characterize lectin-modified liposomes containing insulin and to evaluate the potential of these modified colloidal carriers for oral administration of peptide and protein drugs. Wheat germ agglutinin (WGA), tomato lectin (TL), or Ulex europaeus agglutinin 1 (UEA1) were conjugated by coupling their amino groups to carbodiimide-activated carboxylic groups of N-glutaryl-phosphatidylethanolamine (N-glut-PE). Insulin dispersions were prepared by the reverse-phase evaporation technique and modified with the lectin-N-glut-PE conjugates. Lectin-modified liposomes were characterized according to particles size, zeta potential and entrapment efficiency. The hypoglycemic effect of the lectin-modified pharmacological bioavailability of insulin liposomes modified with WGA, TL and UEA1 were 21.40, 16.71 and 8.38% in diabetic mice as comparison with abdominal cavity injection of insulin, respectively. After oral administration of the insulin liposomes modified with WGA, TL and UEA1 to rats, the relative pharmacological bioavailabilities were 8.47, 7.29 and 4.85%, the relative bioavailability were 9.12, 7.89 and 5.37% in comparison with subcutaneous injection of insulin, respectively. In the two cases, no remarkable hypoglycemic effects were observed with the conventional insulin liposomes. These results confirmed that lectin-modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.

A series of novel L-iso-glutamine derivatives were prepared by condensing of compound 4 with various amino acid methyl esters. These compounds have not been reported in literature, and their chemical structures were confirmed by ESI-MS, IR and NMR.

The crystal structure of (4S)-5-(2-methoxy-2-oxoethylamino)-5-oxo-4-(3,4,5-trimethoxybenzamido) pentanoic acid 5 (C18H24N2O9, Mr=412.39) has been determined by single-crystal X-ray diffraction analysis. The crystal belongs to monoclinic, space group P2(1)/c with a=27.665(9), b=5.1444(16), c=13.907(4) Å, β=98.401(5)º, V=1958.0(11) Å3, Z=4, Dc=1.399 g/cm3, μ=0.113mm－1, F(000)=872, R=0.0606 and wR=0.1405 (I>2σ(I)). The results confirmed that 5 could be assigned to the tautomeric form. The intermolecular hydrogen bonds between O(5)-H(5)…O(7), N(2)-H(2)…O(6) and N(1)-H(1)…O(4) have been observed.

Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesi of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.