Synthesis of Hybrid Cyclopeptides through Enzymatic Macrocyclization

Acknowledgements We thank Dr. G. Mann and Dr. A. Bent for supplying the enzymes and the useful discussions, and Dr. T. Lebl for the useful NMR discussions. This work was supported by the European Research Council (339367), UK Biotechnology and Biological Sciences Research Council (K015508/1), the Wellcome Trust [TripleTOF 5600 mass spectrometer (094476), the MALDI TOF-TOF Analyzer (079272AIA), 700 NMR], and the EPSRC UK National Mass Spectrometry Facility at Swansea University. J.H.N., M.A.J., and N.J.W. are named on patents that have been filed by St. Andrews and Aberdeen Universities to commercialize the enzymes (PatG) and (LynD) used in the study. No income derives from the patent.Peer reviewedPublisher PD

Bypassing the proline/thiazoline requirement of the macrocyclase PatG

Peer reviewedPublisher PD

Lung function in South African children with cystic fibrosis

Objective: To determine the pattern of lung function in stable cystic fibrosis (CF) patients and to investigate the relationship of abnormal lung function to demographic variables, CF genotype and pulmonary colonisation with Pseudomonas aeruginosa (PA)Design: A descriptive study done at the CF clinic at Red Cross War Memorial Children's Hospital in Cape Town.Methods: Data were recorded and pulmonary function testing (PFT) was performed in 42 CF patients.Results: 29 patients (69%) had mild disease,. while 11 (26%) and 2 (5%) had moderate and severe disease respectively. Twenty-four patients (57'%) demonstrated lower airway obstruction (LAO). Patients with moderate or severe disease were significantly older than those with mild disease (13.3 (3.7) years (mean (SD)) compared with 11.1 (3.0) years (t =2.1; P =OM)). PA colonisation status differed significantly with the pattern of lung function (X2 =6.6; P = 0.04) and severity of lung disease (X2=12.6; P =0.002.). Nine (35%) of the 26 patients tested before and after broncbodilator therapy showed a positive response.Conclusion: The majority of patients had mildly impaired or normal lung function, with LAO predominating. A minority of patients were bronchodilator-responsive. PA colonisation may be associated with the development of abnormal lung function and more severe pulmonary disease.

Localization of human breast-carcinoma xenografts using antibodies to carcinoembryonic antigen.

Affinity-purified antibodies to carcinoembryonic antigen (CEA) have been injected into immune-suppressed mice bearing xenografts of human breast tumours. It has been shown that the antibodies localized in the tumours but not in normal tissues. The degree of tumour localization correlates with the amount of tumour CEA, and is unaffected by levels of circulating CEA or CEA/anti-CEA immune complexes

Investigation of the chemocatalytic and biocatalytic valorization of a range of different lignin preparations: The importance of β-O-4 content

A set of seven different lignin preparations was generated from a range of organosolv (acidic, alkaline, ammonia-treated, and dioxane-based), ionic liquid, autohydrolysis, and Kraft pretreatments of lignocelluloses. Each lignin was characterized by 2D HSQC NMR spectroscopy, showing significant variability in the β-O-4 content of the different lignin samples. Each lignin was then valorised using three biocatalytic methods (microbial biotransformation with Rhodococcus jostii RHA045, treatment with Pseudomonas fluorescens Dyp1B or Sphingobacterium sp. T2 manganese superoxide dismutase) and two chemocatalytic methods (catalytic hydrogenation using Pt/alumina catalyst, DDQ benzylic oxidation/Zn reduction). Highest product yields for DDQ/Zn valorization were observed from poplar ammonia percolation-organosolv lignin, which had the highest β-O-4 content of the investigated lignins and also gave the highest yield of syringaldehyde (243 mg L -1 ) when using R. jostii RHA045 and the most enzymatic products using P. fluorescens Dyp1B. The highest product yield from the Pt/alumina hydrogenation was observed using oak dioxasolv lignin, which also had a high β-O-4 content. In general, highest product yields for both chemocatalytic and biocatalytic valorization methods were obtained from preparations that showed highest β-O-4 content, while variable yields were obtained with preparations containing intermediate β-O-4 content, and little or no product was obtained with preparations containing low β-O-4 content