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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
681

Organization and expression of the mouse surfeit gene cluster

Huxley, Clare Marjory Pease January 1989 (has links)
No description available.
682

Membrane enhanced peptide synthesis (MEPS) : process development and application

Chen, Wenqian January 2015 (has links)
Peptides are polymers of amino acids and are better drug candidates than traditional small-molecule compounds due to high specificity and potency. Conventional synthesis methods include Solid Phase Peptide Synthesis (SPPS) and Liquid Phase Peptide Synthesis (LPPS), which have different technical limitations. Significant improvements can be made by a new technology, Membrane Enhanced Peptide Synthesis (MEPS), which integrates nanofiltration into LPPS for the purification of intermediate products. The research work described in this thesis is an outcome of the MemTide consortium (Imperial College London, Institute for Research in Biomedicine (Barcelona) (IRB) and University of Turku) and three companies (Evonik Membrane Extraction Technology (MET) Ltd, Janssen Pharmaceutica and Lonza AG), whose task was to investigate membrane enhanced synthesis for both peptides and oligonucleotides. This research project demonstrates that MEPS is ready for industrial application in terms of technical feasibility and economic performance relative to SPPS and LPPS. The MEPS of two peptides (Fmoc-Arg-Ala-Asp-Ala-NH2 (fully deprotected Fmoc-RADA-NH2) and Pyr-Ser(Bzl)-Ala-Phe-Asp-Leu-NH2 (partially deprotected Pyr-SAFDL-NH2)) is presented in the form of case studies. In the first case study, MEPS of fully deprotected Fmoc-RADA-NH2 was attempted four times. The first three attempts encountered the problem of incomplete coupling after the post-de-Fmoc diafiltration, which was solved by the extended diafiltration (14 wash volumes). At a scale of 10.01 mmol (those in the proof of concept studies were 0.9 and 1.8 mmol), the fourth attempt at MEPS was successful with a purity of 98.5 % and an overall yield of 78.6 % before cleavage and global deprotection. This shows that the integration of nanofiltration into LPPS was technically feasible for obtaining high purity and decent yield of the anchored peptide that were comparable to those of SPPS (85.3 % and 78.3 % respectively before cleavage and global deprotection). In the second case study, a similar research approach was adopted for the partially deprotected Pyr-SAFDL-NH2 and the same problem of incomplete coupling occurred even with increased wash volumes. The cause was found to be residual piperidine in the system after the post-de-Fmoc diafiltration. The solution was to add a base (diisopropylethylamine (DIEA), which was also a reagent in each coupling) into the system during diafiltration to assist the removal of piperidine. At a scale of 33.65 mmol and an anchor concentration of 10.4 weight % in the starting solution, the third attempt at MEPS was successful with a purity of 88.1 % and an overall yield of 71.2 % before cleavage and global deprotection (98.6 % and 72.6 % respectively for SPPS; 100.0 % and 72.4 % respectively for LPPS (by precipitation)). Furthermore, MEPS outperformed SPPS and LPPS (by precipitation) in terms of material cost (8.7 – 13.0 % lower), process time (33.3 – 91.7 % shorter), volumetric efficiency (15.4 – 15.9 % higher) and E-factor (29.3 – 68.8 % lower). The results proved that this novel process is indeed an attractive alternative to SPPS and LPPS (by precipitation) and is ready for industrial application. Encouraged by the positive results from the two case studies, attempts were made to further improve the performance of MEPS before cleavage and global deprotection by reducing the significant yield loss during diafiltration. Peptide synthesis was performed on two alternative anchors (amine-functionalised silica nanoparticles and a branched compound with poly(ethylene glycol) (PEG) arms (PyPEG)), but each had technical limitations during the coupling of amino acids. On the other hand, promising results were obtained from the modelling of MEPS in a two-stage membrane cascade system, as the second membrane served to recover the anchored peptide that permeated through the first one during diafiltration. As a result, the overall yield would increase from 71.2 to 93.8 %, making the new process even more attractive in terms of material cost (23.6 – 33.5 % lower than the single-stage MEPS and SPPS).
683

Studies on the structure and expression of the epidermal factor receptor gene

Whittle, N. R. January 1987 (has links)
No description available.
684

A genetic investigation of methylotrophic metabolism

Paddon, C. J. January 1983 (has links)
No description available.
685

Botulinum neurotoxins and their neuronal acceptors

Williams, R. S. January 1984 (has links)
No description available.
686

The multiple molecular forms of acetylcholinesterease in skeletal muscles : a function analysis

Lai, J. Y. W. January 1985 (has links)
No description available.
687

Polyoma virus : the immunological and biochemical studies of early and late gene production

Street, A. J. January 1986 (has links)
No description available.
688

The molecular biology of the interferon response : the 1-8/9-27 gene family

Brasnett, Adrian H. January 1991 (has links)
No description available.
689

The biogenesis of secretory organelles in a neuroendocrine cell line

Cramer, Louise Pauline January 1991 (has links)
No description available.
690

Characterisation and localisation of the nicotinic acetylcholine and benzodiazepine receptors in the brain

Lang, B. January 1982 (has links)
No description available.

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