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ABSTRACT: Breaking down barriers: A rapid, inexpensive preparation of the structurally complex mycobacterial N-glycolyl Lipid I, Lipid II, and their analogues from a range of different synthetic N-glycolyl and N-glycinyl Park's nucleotides is described. The biotransformations were catalyzed by a readily available biocatalyst obtained from a bacterial cell-free membrane fraction. The unnatural N-glycinyl Lipid II was found to be a substrate of Mycobacterium tuberculosis (Mtb) transglycosylase, PonA, and N-glycolyl Lipid I was a weak inhibitor against PonA.
Chemistry 12/2012; · 5.93 Impact Factor
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ABSTRACT: A feasible synthetic approach toward the Mycobacterium tuberculosis (Mtb) N-glycolyl lipid II-like molecule 1 is described. Compound 1 bears pendant undecaprenol and l-lysin moieties instead of the naturally occurring decaprenol and meso-diaminopimelic acid, which are not readily available. Functionalization of 1 with a fluorophore on the peptide side chain gave 14, which was found to be recognized as an Mtb TGase substrate. This result suggests it has tremendous utility for mechanistic studies, the characterization of mycobacterial enzymes, and mycobacterial TGase inhibitor evaluation.
Organic Letters 09/2011; 13(19):5306-9. · 5.86 Impact Factor
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ABSTRACT: A new synthetic approach toward the bacterial transglycosylase substrates, Lipid II (1) and Lipid IV (2), is described. The key disaccharide was synthesized using the concept of relative reactivity value (RRV) and elaborated to Lipid II and Lipid IV by conjugation with the appropriate oligopeptides and pyrophosphate lipids. Interestingly, the results from our HPLC-based functional TGase assay suggested Lipid IV has a higher affinity for the enzyme than Lipid II.
Organic Letters 07/2011; 13(17):4600-3. · 5.86 Impact Factor
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Ting-Jen Rachel Cheng,
Ying-Ta Wu,
Shih-Ting Yang,
Kien-Hock Lo,
Shao-Kang Chen,
Yin-Hsuan Chen,
Wen-I Huang,
Chih-Hung Yuan,
Chih-Wei Guo,
Lin-Ya Huang, Kuo-Ting Chen,
Hao-Wei Shih,
Yih-Shyun E Cheng,
Wei-Chieh Cheng,
Chi-Huey Wong
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ABSTRACT: To identify new transglycosylase inhibitors with potent anti-methicillin-resistant Staphylococcus aureus (MRSA) activities, a high-throughput screening against Staphylococcus aureus was conducted to look for antibacterial cores in our 2M compound library that consists of natural products, proprietary collection, and synthetic molecules. About 3600 hits were identified from the primary screening and the subsequent confirmation resulted in a total of 252 compounds in 84 clusters which showed anti-MRSA activities with MIC values as low as 0.1 μg/ml. Subsequent screening targeting bacterial transglycosylase identified a salicylanilide-based core that inhibited the lipid II polymerization and the moenomycin-binding activities of transglycosylase. Among the collected analogues, potent inhibitors with the IC(50) values below 10 μM against transglycosylase were identified. The non-carbonhydrate scaffold reported in this study suggests a new direction for development of bacterial transglycosylase inhibitors.
Bioorganic & medicinal chemistry 10/2010; 18(24):8512-29. · 2.82 Impact Factor
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ABSTRACT: The development of iminocyclitol-based small molecule libraries against a bacterial TGase is described. An iminocyclitol was conjugated with a pyrophosphate mimic using either a 1,3-dipolar cycloaddition or reductive amination reaction, which was then condensed with a variety of lipophilic carboxylic acids in an amide bond coupling to generate a desired molecular library. With assistance of microtiter plate-based combinatorial chemistry and in situ screening, a potential inhibitor, the first potent iminocyclitol-based inhibitor against bacterial TGases was efficiently developed.
Organic & Biomolecular Chemistry 06/2010; 8(11):2586-93. · 3.70 Impact Factor
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ABSTRACT: Van der Woude syndrome, characterized by lip pits and cleft lip/ palate, presents with variable expressions. This retrospective study was designed to obtain a better understanding of its clinical pattern in Taiwanese patients.
Of 13,147 cleft patients treated at the Chang Gung Craniofacial Center from 1976 to 2004, there were 64 with Van der Woude syndrome. Clinical expressions and family histories were collected and analyzed.
The male to female ratio was 1:1. The majority had complete cleft types. Severe cleft was found among the patients, with 52% having bilateral cleft lip and palate, 31% having unilateral cleft lip and palate, and 17% having isolated cleft palate. A positive family history was found in 53.1% of the patients. The size, shape, location, and depth of the pits varied among patients.
Clinical presentations did not always parallel those reported in the literatures. These differences warrant further investigation.
The Cleft Palate-Craniofacial Journal 12/2007; 44(6):649-52. · 0.82 Impact Factor
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ABSTRACT: We report an unusual cause of acute total airway obstruction after aspiration of a dislodged tube that was separated from its metallic connector. A 5-year-old boy had an emergence agitation and bucking to the endotracheal tube with a vigorous bite before extubation of the trachea. The whole uncuffed endotracheal tube was aspirated deep into the lower trachea causing laryngotracheal obstruction. The patient showed sudden oxygen desaturation and was then in an immediate life-threatening airway obstruction. We could not rescue oxygenation and were unable to establish a patent airway. Mask ventilation failed to relieve the progressive of hypoxemia. Immediate extraction of the tube using a pair of Magill's forceps before irreversible exacerbation was performed. We discuss our experience and the importance of prompt decision making and management for the extraction of the dislodged tube.
Chang Gung medical journal 08/2003; 26(7):515-9.
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ABSTRACT: Background
Plexiform neurofibromatosis is a feature of von Recklinghausen's disease. Head and neck lesions may produce varying degrees of cosmetic and functional deformity. However, life-threatening hemorrhage into facial plexiform neurofibromas has not been previously reported.Method
We report two patients with von Recklinghausen's disease who experienced massive hemorrhage into facial neurofibromas, one following a blunt injury and the other without a known initiating event.ResultsConservative management did not stop the hemorrhage into facial neurofibromas in either instance. Surgical exploration was mandated for hemorrhage control and evacuation of blood clots. Hemostasis was attained by a combination of hypotensive anesthesia and chromic catgut suture ligatures.Conclusions
These case reports demonstrate a potentially lethal complication in patients with facial plexiform neurofibroma. Where a competent and experienced interventional neuroradiologist is not available, surgical exploration should be undertaken to control bleeding. © 1997 John Wiley & Sons, Inc. Head Neck19: 158–162, 1997.
Head & Neck 02/1997; 19(2):158 - 162. · 2.40 Impact Factor
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ABSTRACT: Over a period of 17 years, gradual modifications of the Millard rotation advancement cheiloplasty were made based on the experience of treating a large number of clefts seen in the Chang Gung Craniofacial Center. Emphasis is made on primary nasal correction and definitive repair of the lip. Some of the important aspects of this repair include the following: (1) no dissection over the maxilla; (2) primary nasal correction; (3) lining the pyriform area with an inferior turbinate mucosal flap; (4) complete wound closure of all areas to prevent contracture; (5) alar transfixion sutures for creating an alar groove and fixation of the lower lateral cartilage; (6) reconstruction of deficient vermilion on the cleft side of the Cupid's bow, creating a parallel “red line” and “white skin roll”; (7) dissection of muscle and skin to minimize horizontal scars extending beneath or around the ala; (8) no “back-cuts”, using a small triangular skin flap above the =ldwhite skin roll” whenever necessary to achieve adequate rotation without distortion of the philtral column; (9) postoperative splinting with a silicone nasal conformer. Preoperative evaluation and measurement of the pathological deformity will help achieve a better result. Also, preoperative measurements are useful in evaluation of postoperative results.
Operative Techniques in Plastic and Reconstructive Surgery.
