Laser-raman spectroscopic study of carbohydrates: 1-thio-β-d-hexopyranosides

Some β-d-hexopyranosides of 1-thio-d-glucose, 2-acetamido-2-deoxy-1-thio-d-glucose, and 1-thio-d-galactose were examined by laser-Raman spectroscopy. An anomeric CH bending vibration was found at 891 ± 7 cm^-1 for all compounds investigated; thus, the anomers of these sugars can be differentiated by Raman spectroscopy. The N-acetyl group and carboxyl group can also be detected by Raman spectroscopy. Unlike protein samples, the carbohydrates in aqueous solution yield less useful information from Raman spectra than in the solid state; this is due to the extensive overlapping of carbohydrate OH bands with water OH bands.     

Micellization phenomena of amphiphilic block copolymers based on methoxy poly(ethylene glycol) and either crystalline or amorphous poly(caprolactone-b-lactide)

This study focuses on the aggregation behavior of the biodegradable amphiphilic block copolymers based on methoxy poly(ethylene glycol) (mPEG) as a hydrophilic block and either crystalline poly(caprolactone-b-l-lactide) (P(CL-LLA)) or amorphous poly(caprolactone-b-D,L-lactide) (P(CL-DLLA)) as a hydrophobic block. These block copolymers have a strong tendency to form micelles in aqueous medium, with very low critical micelle concentrations (CMCs). The CMC of P(CL-LLA)-b-mPEG is higher than that of P(CL-DLLA)-b-mPEG when the mPEG block has the same molecular weight. Furthermore, the partition equilibrium coefficient (K(v)) of pyrene in the micellar solution of P(CL-LLA)-b-mPEG copolymer was lower than that of P(CL-DLLA)-b-mPEG copolymer when the mPEG block was the same length. These differences were believed to be related to the physical state of the core-forming blocks, i.e., the crystalline P(CL-LLA) block and the amorphous P(CL-DLLA) block. The TEM images showed that micelles formed by P(CL-LLA)-b-mPEG assembled in a cylindrical morphology, whereas those formed by P(CL-DLLA)-b-mPEG took a classical spherical shape. In addition, with differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) analyses, it is believed that the crystallization tendency of the core-forming blocks is the main factor governing the morphology of micelles in water. A possible mechanism for the cylindrical assembly morphology was discussed.     

An arabinogalactan isolated from the stems of Cistanche deserticola induces the proliferation of cultured lymphocytes

A purified polysaccharide ACDP-2 was isolated from water extract of the stems of Cistanche deserticola. Chemical and spectroscopic analyses indicated that ACDP-2 is a highly branched arabinogalactan polymer that composes of linked d-galactopyranose and d-glucopyranose, which contains predominantly a branching point at the 6-carbon. The branched side-chains compose of terminal-, 1,5-, and 1,3,5-linked arabinofuranosyl residues. ACDP-2 showed an effect in stimulating the immune response, which when applied onto the cultured mouse lymphocytes induced the cell proliferation in a dose-dependent manner.     

Neurotrophins,but not depolarization,regulate substance P expression in the developing optic tectum

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve‐dependent regulation of a substance P‐like immunoreactive (SP‐ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6‐cyano‐7‐nitroquinoxaline‐2,3 dione (CNQX) did not affect the percent of SP‐ir cells in the developing tectum. Treatment with d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (d‐AP‐5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) produced increases in SP‐ir cells in the treated lobes of normal animals, which were significant in the case of NT‐4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve‐transected tadpoles. These changes in the percent of SP‐ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT‐4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide‐expressing population of cells. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 131–149, 2001     

Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold.

A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificity, that is, show a preference for the same P(1) residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both the S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability.     

The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy.     

Fine mapping of the recessive genic male-sterile gene (Bnms1) in Brassica napus L.

A recessive genic male sterility (RGMS) system, S45 AB, has been developed from spontaneous mutation in Brassica napus canola variety Oro, and is being used for hybrid cultivar development in China. The male sterility of S45 was controlled by two duplicated recessive genes, named as Bnms1 and Bnms2. In this study, a NIL (near-isogenic line) population from the sib-mating of S45 AB was developed and used for the fine mapping of the Bnms1 gene, in which the recessive allele was homozygous at the second locus. AFLP technology combined with BSA (bulked segregant analysis) was used. From a survey of 2,560 primer combinations (+3/+3 selective bases), seven AFLP markers linked closely to the target gene were identified, of which four were successfully converted to sequence characterized amplified region (SCAR) markers. For further analysis, a population of 1,974 individuals was used to map the Bnms1 gene. On the fine map, Bnms1 gene was flanked by two SCAR markers, SC1 and SC7, with genetic distance of 0.1 cM and 0.3 cM, respectively. SC1 was subsequently mapped on linkage group N7 using doubled-haploid mapping populations derived from the crosses Tapidor × Ningyou7 and DH 821 × DHBao 604, available at IMSORB, UK, and our laboratory, respectively. Linkage of an SSR marker, Na12A02, with the Bnms1 gene further confirmed its location on linkage group N7. Na12A02, 2.6 cM away from Bnms1, was a co-dominant marker. These molecular markers developed from this research will facilitate the marker-assisted selection of male sterile lines and the fine map lays a solid foundation for map-based cloning of the Bnms1 gene.     

The genetic basis of flowering time and photoperiod sensitivity in rapeseed (Brassica napus L.)

The objective of this study was to dissect the genetic control of days to flowering (DTF) and photoperiod sensitivity (PS) into the various components including the main-effect quantitative trait loci (QTLs), epistatic QTLs and QTL-by-environment interactions (QEs). Doubled haploid (DH) fines were produced from an F1 between two spring Brassica napus cultivars Hyola 401 and Q2. DTF of the DH lines and parents were investigated in two locations, one location with a short and the other with a long photoperiod regime over two years. PS was calculated by the delay in DTF under long day as compared to that under short day. A genetic linkage map was constructed that comprised 248 marker loci including SSR, SRAP and AFLP markers. Further QTL analysis resolved the genetic components of flowering time and PS into the main-effect QTLs, epistatic QTLs and QEs. A total of 7 main-effect QTLs and 11 digenic interactions involving 21 loci located on 13 out of the 19 linkage groups were detected for the two traits. 3 main-effect QTLs and 4 pairs of epistatic QTLs were involved in QEs conferring DTF. One QTL on linkage group (LG) 18 was revealed to simultaneously affect DTF and PS and explain for the highest percentage of the phenotypic variation. The implications of the results for B. napus breeding have been discussed.