Evaluation of amylose used as a drug delivery carrier.

The enzyme-dependent conjugates of indomethacin and amylose (Am-IND) were synthesized at room temperature using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent and 4-(N,N'-dimethylamino) pyridine (DMAP) as a catalyst. Their structures were characterized by FTIR and (1)H NMR analyses, and the results indicated that the IND residues were conjugated with amylose backbones through ester bonds. For the conjugate with a lower IND content, the better water absorption property was advantageous for enzymes diffusing into the swollen conjugate, resulting in biodegradation of the conjugates and release of IND. In vitro biodegradation evaluation indicated that the Am-IND conjugates were biodegraded in the simulated media of the intestines. In vitro drug release experiments showed that the Am-IND conjugates exhibited a sustained release behavior in the simulated media of the intestines, while IND was hardly released in the simulated gastric fluid. These features provide a great opportunity to use the conjugates as a prodrug for intestinally targeted and controlled release of IND through oral administration. This study may lead to the development of effective methods for utilizing amylose as a new drug delivery carrier.

Side reactions in the pyroglutamic acid-7-amino-4-methylcoumarin synthesis.

N-Formylpyroglutamic acid-7-amido-4-methylcoumarine and pyroglutamyl-pyroglutamic acid-7-amido-4-methylcoumarin are the major products in the synthesis of pyroglutamic acid-7-amido-4-methylcoumarin by phosphorus pentachloride in dimethylformamide and dicyclohexylcarbodiimide under pyridine activation.

Structure of a 16 kDa integral membrane protein that has identity to the putative proton channel of the vacuolar H(+)-ATPase.

A 16 kDa protein has been isolated in a homogeneous form as the major component of a paracrystalline paired membrane structure closely resembling the gap junction. The primary structure of this protein from arthropod and vertebrate species has been determined by protein and cDNA sequencing. The amino acid sequences are highly conserved and virtually identical to the amino acid sequence of the proteolipid subunit of the vacuolar H(+)-ATPases. The disposition of the protein in the membrane has been studied using proteases and the N,N'-dicyclohexylcarbodiimide reactive site identified. These data, together with secondary structure predictions, suggest that the 16 kDa protein is for the most part buried in the membrane, arranged in a bundle of four hydrophobic alpha-helices. Using computer graphics, a model has been constructed based on this arrangement and on the electron microscopic images of the paracrystalline arrays.