Dynamic selection of novel vancomycin N-terminal derivatives by resin-bound reversed D-Ala-D-Ala.

The most attractive advantage of dynamic combinatorial chemistry (DCC) is that it can screen the compound library as soon as compounds are synthesized. However, it is very difficult to analyze a dynamic combinatorial library with free probes using the state-of-the art analysis technologies. We report herein a method that uses a resin-immobilizing reversed peptide probe to screen vancomycin derivatives and provides a solution to this problem.

Genomic structure and mutational analysis of the human KIF1Balpha gene located at 1p36.2 in neuroblastoma.

KIF1a is a member of the kinesin superfamily proteins that are microtubule-dependent molecular motors involved in important intracellular functions such as organelle transport and cell division. We previously determined the structure of the human KIF1Bbeta gene, which was found to be a homologue of the murine Kif1bbeta, and demonstrated that the human KIF1Bbeta is a causative gene of Charcot-Marie-Tooth disease type 2A although we did not prove that it is a tumor suppressor gene of neuroblastoma. Here, we identified another isoform of the human KIF1B gene, KIF1Balpha. The KIF1Balpha and KIF1Bbeta are alternative splicing products of the KIF1B gene located on 1p36.2. The KIF1Balpha is distinct from KIF1Bbeta in the C-terminal cargo-binding domain; however, they have the same N-terminal motor domain. We found that the transcript of approximately 7.8 kb of KIF1Balpha was expressed in several tissues, especially in skeletal muscle, by Northern blot analysis. To determine whether this gene is one of the candidate tumor suppressor genes for neuroblastoma (NB) or other pediatric solid tumors, we performed mutational screening of KIF1Balpha in 25 NB, 9 rhabdomyosarcoma, 12 Ewing sarcoma and 24 other pediatric solid tumor cell lines. Using RT-PCR single-strand conformation polymorphism analysis and direct sequencing we detected a missense mutation (M807I) in 1 NB cell line (SK-N-SH), 3 silent mutations in 2 NB cell lines and 1 primitive neuroectodermal tumor cell line, respectively. RT-PCR analysis revealed that KIF1Balpha was obviously expressed in almost all of the tumor cell lines examined except NB-1. Furthermore, real-time quantitative RT-PCR showed that there was no significant difference in KIF1Balpha expression between 14 early-stage (stage I and II) and 14 advanced-stage (stage III and IV) NB fresh tumor specimens. These results suggest that KIF1Ba in addition to KIF1Bbeta may not be a candidate tumor suppressor gene for NB.

Synthesis of poly(p-dioxanone) catalyzed by Zn L-lactate under microwave irradiation and its application in ibuprofen delivery.

Microwave-assisted ring-opening polymerization (ROP) of p-dioxanone (PDO) catalyzed by Zn L-lactate (Znlac(2)) was investigated and the purified product was characterized by (1)H-NMR. When the ROP of PDO was carried out at 100 degrees C for 6.5 h, the viscosity-average molecular weight (M(v)) of poly(p-dioxanone) (PPDO) reached 53.2 kg/mol. The kinetics of ring-opening polymerization of PDO under microwave irradiation were investigated and the polymerization reaction was accurately first-order with respect to monomer concentration. The reaction rate was greatly accelerated by microwave irradiation, compared with conventional heating. The resultant PPDO was used as carrier and drug-release systems were prepared using ibuprofen (IBU) as model drug with 10, 15 and 20% loading. The release behavior of the systems was investigated in phosphate buffer solution at 37 degrees C and the release of IBU from the system was sustained and steady. The resultant PPDO could be well used as the carrier for the delivery drug.