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Biomedical subjects

Gang Liu

Publications and source records attributed to Gang Liu.

247 records · Page 14Linked to original sources
PubMedDate not supplied

"Meshed-Bag Gathered-Bunch" method for solid-phase synthesis of small molecular diverse compounds.

A new "Meshed-Bag Gathered-Bunch" technology for the solid-phase synthesis of chemical libraries was developed. Using such technology, we synthesized muramyl dipeptide mimetics including derivatives at the N- and C-terminus, cyclic muramyl dipeptide mimetics, muramyl dipeptide and Tuftsin's analogue conjugates. The advantages of such a method include ease of manufacture, low unit cost of production, the physical encoding method, and the compatibility with both parallel and "split-mix" approaches.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Solid-phase synthesis of O-glycosylated Nalpha-Fmoc amino acids and analysis by high-resolution magic angle spinning NMR.

Direct O-glycosylation of amino acids bound to TentaGel resin with a number of glycosyl trichloroacetimidate donors results in high yields. The glycosylation reaction can be easily monitored by analyzing the bead-bound amino acids with high-resolution magic angle spinning (HR-MAS) NMR. These studies pave a new way for the construction of "one-bead one-compound" O-glycopeptide libraries with standard amino acid building blocks and appropriate glycosyl trichloroacetimidate donors.

Acetamides↗
PubMedDate not supplied

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro.

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO2)2 to m-Ar(NH2)2 was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC50 values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.

Animals↗
PubMedDate not supplied

Conformational studies of resin-bound vancomycin and the complex of vancomycin and Ac2-L-Lys-D-Ala-D-Ala.

The molecular target of vancomycin, a commonly used glycopeptide antibiotic, is the D-Ala-D-Ala dipeptide subunit on the bacterial cell wall. The molecular basis of interaction between vancomycin and D-Ala-D-Ala in solution is well-known. However, there is no structural data on vancomycin, and its interaction with D-Ala-D-Ala when the drug is tethered to a solid support. In this Article, vancomycin was directly coupled onto TentaGel or PEGA resin through its C terminus. High-resolution magic angle spinning NMR studies indicated that conformation of PEGA bead-bound vancomycin is identical to that of the free drug. Broadening and shifts of the same proton resonances were observed in solution-phase vancomycin or PEGA-bound vancomycin when complexed with Ac(2)-L-Lys-D-Ala-D-Ala. This study demonstrates that bead-bound molecules can behave the same as solution-phase molecules in terms of molecular interaction with its target molecule, thus validating the on-bead screening approach of the "one-bead-one-compound" combinatorial library method.

Combinatorial Chemistry Techniques↗
PubMedDate not supplied

Multistep parallel synthesis of substituted 5-aminobenzimidazoles in solution phase.

An efficient solution-phase parallel synthesis of multisubstituted 5-aminobenzimidazoles is described. The two fluorine atoms of 1,5-difluoro-2,4-dinitrobenzene (DFDNB) are sequentially and quantitatively replaced by nucleophiles. Simultaneous reduction of aromatic m-dinitro groups by Pd-C/HCOONH(4) results in 2,4,5-benzenetriamines, which are continuously condensed with aldehydes to successfully construct the benzimidazole ring without additional oxidants. The free aromatic amino group is further modified by anhydrides, isocyanates, isothiocyanates, and sulfonyl chlorides. All the reactions involved here are highly effective in giving the desired products at room temperature. Four diversity points are introduced in the final products.

Journal Article↗
PubMedDate not supplied

Solution-phase parallel synthesis of a 1,2,7-trialkyl-1H-imidazo[4,5-g]quinoxalin-6-ol library scaffold.

This paper describes solution-phase parallel synthesis of a library with a novel 1,2,7-trialky-1H-imidazo[4,5-g]quinoxalin-6-ol scaffold and three points of diversity. The library is prepared using 1,5-difluoro-2,4-dinitrobenzene as the starting material and commercially available chemicals as the building blocks. A new, inexpensive, and practical apparatus for parallel filtration is also described.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library.

A 10-mer overlapping peptide library has been synthesized for screening and identification of linear B-cell epitopes of severe acute respiratory syndrome associated coronavirus (SARS-CoV), which spanned the major structural proteins of SARS-CoV. One hundred and eleven candidate peptides were positive according to the result of PEPscan, which were assembled into 22 longer peptides. Five of these peptides showed high cross-immunoreactivities (approximately 66.7 to 90.5%) to SARS convalescent patients' sera from the severest epidemic regions of the China mainland. Most interestingly, S(471-503), a peptide located at the receptor binding domain (RBD) of SARS-CoV, could specifically block the binding between the RBD and angiotensin-converting enzyme 2, resulting in the inhibition of SARS-CoV entrance into host cells in vitro. The study demonstrated that S(471-503) peptide was a potential immunoantigen for the development of peptide-based vaccine or a candidate for further drug evaluation against the SARS-CoV virus-cell fusion.

Amino Acid Sequence↗
PubMedDate not supplied

Benzofused tricycles based on 2-quinoxalinol.

This paper describes our recent efforts to synthesize novel compound scaffolds integrating 2-quinoxalinol with privileged structures of 1,3-dihydro-benzoimidazol-2-one, 1,3-dihydro-benzoimidazole-2-thione, 3-hydroxy-1H-quinoxalin-2-one, 2H-benzo[1,4]oxazin-3-ol, 2H-benzo[1,4]thiazin-3-ol, and 1,3,4,5-tetrahydro-benzo[1,4]diazepin-2-one, respectively. Eight novel benzofused tricycles and their substituent diversity points were developed. These include pyrazino[2,3-g]quinoxaline-2,8-diol (I), 3-hydroxy-6,8,9,10-tetrahydro-1,4,6,10-tetraaza-cyclohepta[b]naphthalen-7-one (II), 6-hydroxy-4H-1-oxa-4,5,8-triaza-anthracen-3-one (III), 6-hydroxy-4H-1-thia-4,5,8-triaza-anthracen-3-one (IV), 6-hydroxy-1,1-dioxo-1,4-dihydro-2H-1lambda(6)-thia-4,5,8-triaza-anthracen-3-one (V), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxalin-2-one (VI), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxaline-2-thione (VII), and 7-hydroxy-1,4-dihydro-pyrazino[2,3-g]quinoxaline-2,3-dione (VIII). This strategy of integrating two benzofused privileged structures into one molecule may provide a greater chance for the discovery of novel lead compounds.

Anthracenes↗
PubMedDate not supplied

Synthesis of diverse benzo[1,4]oxazin-3-one-based compounds using 1,5-difluoro-2,4-dinitrobenzene.

This paper discusses the synthesis of benzo[1,4]oxazin-3-one-based compounds from 1,5-difluoro-2,4-dinitrobenzene (1), including benzo[1,4]oxazin-3-ones (5-11) and five novel benzo[1,4]oxazin-3-one-based tricycles: 6-hydroxy-4H-1-oxa-4,5,8-triazaanthracen-3-one (14), 3,8-dihydro-5-oxa-1,3,8-triazacyclopenta-[b]-naphthalene-7-one (15, 17, 21), 3,8-dihydro-5-oxa-1,2,3,8-tetraazacylopenta[b]-naphthalene-7-one (16, 20), 3,8-dihydro-1H-5-oxa-1,3,8-triazacyclopenta[b]-naphthalene-2,7-dione (18, 22), and 5,8-dihydro-4H-1-oxa-4,5,8-triazaanthracene-3,6,7-trione (19). Finally, a chemical library based on 15 was synthesized in parallel solution-phase reactions.

Benzoxazines↗
PubMedDate not supplied

Solution-phase parallel synthesis of 3,5,6-substituted indolin-2-ones.

A practical and efficient new parallel method has been developed for the synthesis of 3-substituted indolin-2-ones with a large variety of substituents at the 5- and 6-positions using 1,5-difluoro-2,4-dinitrobenzene. This 3,5,6-substituted indolin-2-one skeleton possesses three points of diversification and, thus, affords new opportunities for identification and optimization of leads in drug discovery.

Combinatorial Chemistry Techniques↗
PubMedDate not supplied

Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously.

OBJECTIVES: The aim of this study was to compare the analgesic effects and pharmacokinetics of epidural versus intravenous administration of low doses of ketamine. METHODS: 45 patients scheduled for selective gastrectomy were randomly assigned into 3 groups: 0.5mg/kg ketamine administered epidurally (Kepi group), 0.5 mg/kg ketamine administered intravenously (Kiv group), or 10ml normal saline administered epidurally (Ctr group). Analgesic effects were evaluated using Visual Analog Scale (VAS) pain scores at rest, time to first request for analgesic (TFA), and subsequent morphine consumption. The plasma concentration of ketamine was measured with high performance liquid chromatography (HPLC) in the Kepi and Kiv groups. The elimination half-life of ketamine was calculated. RESULTS: Patients in the Kepi group had significantly lower VAS pain scores, longer TFA, and lower morphine consumption than patients in the Kiv or Ctr groups. Compared with intravenous administration, epidural administration of ketamine resulted in higher plasma concentrations from 90 minutes to 48 hours after injection, and much longer elimination half-life of ketamine, but a lower maximum plasma concentration of ketamine. CONCLUSION: The results suggest that epidural administration of a low dose of ketamine provides more effective analgesic effects as seen post-operatively than intravenous administration. The prolonged half-life and high plasma sustained concentration of epidural ketamine might account for the difference in analgesic effects.

Adult↗
PubMedDate not supplied

Isolation and characterization of fourteen novel putative and nine known target genes of the p53 family.

p53, a transcription factor, exerts its tumor suppressor activity by regulating a diverse array of genes involved in the control of the cell cycle, apoptosis, differentiation, and DNA repair. Previously, we and others have found that p53 contains multiple separate functional domains, each of which has a unique contribution to the activity of p53 in inducing cell cycle arrest and apoptosis, probably via differential regulation of target genes. We and others have also found that the p53 family members, that is, p53, p63, and p73, are all capable of inducing cell cycle arrest and apoptosis and regulate both common and unique target genes. Here, we used Affymetrix GeneChip assay and Northern blot analysis to determine whether some known target genes are regulated by various p53 mutants, which are active in inducing cell cycle arrest, apoptosis, or both, and to identify novel target genes regulated by the p53 family. We found that various p53 functional domains control the induction of a target gene, which may be responsible for the unique activity of a given functional domain in inducing cell cycle arrest or apoptosis. In addition, we identified fourteen potential novel target genes that are differentially regulated by various p53 family members. Therefore, the regulation of a known target gene by a defined p53 mutant can be used to classify the role of the target gene in p53 tumor suppression and the identification of these fourteen potential novel target genes of the p53 family can lead to uncover the signaling pathway to which a p53 family member functions in tumor suppression (p53) and in development (p63 and p73).

Apoptosis↗