FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2952100523> ?p ?o ?g. }

• W2952100523 abstract "The work presented herein applies advanced techniques in an ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) to study one of the most amyloidogenic amyloid proteins – human islet amyloid polypeptide (hIAPP) and we also demonstrate alternative analytical techniques for proteomics.Exploring the aggregation and inhibition pathways of amyloid proteins is critical for future therapeutic development. Previous studies demonstrated the early, soluble oligomers of amyloid proteins are more toxic to neuro cells than mature amyloid fibrils due to their ability to penetrate and destroy neuro cell membranes. Current analytical techniques for amyloid protein studies, including nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectrometry, transmission electron microscopy (TEM), and atomic force microscopy (AFM), are difficult to perform as they require molecular isolation and focus on studying individual target early oligomers from a mixtures of oligomers. Previous literature, however, has demonstrated the ability of MS in observing as well as isolating a specific oligomer from an in vitro amyloid protein sample. Thus, MS has been applied together with electron-based dissociation technique in this thesis to determine the aggregation as well as inhibition pathways of hIAPP.The results herein demonstrate the region around Gly-33 and Ser-34 of hIAPP is critical for hIAPP aggregation since it is the minimum interaction region between the two hIAPP units which was shown by the electron-based dissociation spectra of the dimer as well as the trimer of hIAPP. hIAPP has also shown to be deamidated rapidly within a month at Asn-21, Asn-22, and Asn-35 residues, regarding there are seven potential deamidation sites within the sequence. The deamidated hIAPP species with iso-aspartic acid residue products at the deamidation sites shows a significant change in the amyloid fibril morphology which may help to explain the previously observed acceleration of aggregation rate by inducing 5% of deamidated hIAPP into non-deamidated hIAPP solution.The methodologies applied in studying the aggregation pathway of hIAPP are further used to explore the inhibition pathways between hIAPP and potential inhibitors. From the results, two different inhibition pathways are proposed to effectively prevent the formation of hIAPP fibrils. Inhibitors interacting specifically at the critical aggregation region around Gly-33 and Ser-34, are shown to prevent the formation of hIAPP fibrils by forming hetero-complexes (a complex composes of hIAPP and inhibitor). The alternative inhibition pathway requires an inhibitor which interacts non-specifically with hIAPP and triggers the formation of non-toxic amorphous aggregates faster than the generation of normal, toxic hIAPP oligomers. These two proposed inhibition pathways show an effective inhibition effect on formation of hIAPP fibrils, however, only the non-specifically interaction pathway was effective in preventing the aggregation of the deamidated from hIAPP since the protein sequence as well as structure are distorted in the deamidated hIAPP which significantly affects the specific interaction between the deamidated hIAPP and inhibitors.The in vitro studies propose the potential aggregation and inhibition pathways for hIAPP; it is critical, but unfortunately very challenging, to study these molecular interactions in vivo due to the solvents and column chemistry required by the current liquid chromatography (LC) approach which is necessary for complex mixture studies. In order to study the in vivo molecular interactions, an alternative analytical technique, therefore, is required.Herein, two dimensional mass spectrometry (2DMS) is applied to study proteomic samples ranging from standard protein digests to whole cell lysate digest without online LC separation. Various sample preparation and 2DMS acquisition methods have been applied to optimise the proteomic outputs from 2DMS. From the results, 2DMS shows a similar capability in studying proteomics compared to the standard LC tandem MS (MS/MS) techniques. The peptides assigned in 2DMS experiments are more hydrophilic, basic, and short, which are complementary to those assigned in the LC MS/MS technique, thus more proteins can be covered by combining the results obtained from 2DMS and LC MS/MS, in which a deeper proteome coverage is achieved. 2DMS is shown to be a viable alternative analytical tool for proteomics, in which is also potential for the in vivo study of molecular interactions in the coming future.The final section of this thesis provides a conclusion on all the works that have been demonstrated herein and discusses the future research which we needed to improve/enhance the current knowledge on amyloid protein studies using MS as well as 2DMS for proteomics." @default.
• W2952100523 created "2019-06-27" @default.
• W2952100523 creator A5025954312 @default.
• W2952100523 date "2018-07-01" @default.
• W2952100523 modified "2023-09-27" @default.
• W2952100523 title "Advanced new technologies for protein analysis by mass spectrometry" @default.
• W2952100523 hasPublicationYear "2018" @default.
• W2952100523 type Work @default.
• W2952100523 sameAs 2952100523 @default.
• W2952100523 citedByCount "0" @default.
• W2952100523 crossrefType "dissertation" @default.
• W2952100523 hasAuthorship W2952100523A5025954312 @default.
• W2952100523 hasConcept C12554922 @default.
• W2952100523 hasConcept C136238340 @default.
• W2952100523 hasConcept C142724271 @default.
• W2952100523 hasConcept C162356407 @default.
• W2952100523 hasConcept C170552419 @default.
• W2952100523 hasConcept C178790620 @default.
• W2952100523 hasConcept C179104552 @default.
• W2952100523 hasConcept C185592680 @default.
• W2952100523 hasConcept C27523624 @default.
• W2952100523 hasConcept C2776403692 @default.
• W2952100523 hasConcept C2776982924 @default.
• W2952100523 hasConcept C2777633098 @default.
• W2952100523 hasConcept C2779134260 @default.
• W2952100523 hasConcept C2779546866 @default.
• W2952100523 hasConcept C2780642029 @default.
• W2952100523 hasConcept C2909607560 @default.
• W2952100523 hasConcept C2994168385 @default.
• W2952100523 hasConcept C3019447875 @default.
• W2952100523 hasConcept C43617362 @default.
• W2952100523 hasConcept C55493867 @default.
• W2952100523 hasConcept C71924100 @default.
• W2952100523 hasConcept C86803240 @default.
• W2952100523 hasConceptScore W2952100523C12554922 @default.
• W2952100523 hasConceptScore W2952100523C136238340 @default.
• W2952100523 hasConceptScore W2952100523C142724271 @default.
• W2952100523 hasConceptScore W2952100523C162356407 @default.
• W2952100523 hasConceptScore W2952100523C170552419 @default.
• W2952100523 hasConceptScore W2952100523C178790620 @default.
• W2952100523 hasConceptScore W2952100523C179104552 @default.
• W2952100523 hasConceptScore W2952100523C185592680 @default.
• W2952100523 hasConceptScore W2952100523C27523624 @default.
• W2952100523 hasConceptScore W2952100523C2776403692 @default.
• W2952100523 hasConceptScore W2952100523C2776982924 @default.
• W2952100523 hasConceptScore W2952100523C2777633098 @default.
• W2952100523 hasConceptScore W2952100523C2779134260 @default.
• W2952100523 hasConceptScore W2952100523C2779546866 @default.
• W2952100523 hasConceptScore W2952100523C2780642029 @default.
• W2952100523 hasConceptScore W2952100523C2909607560 @default.
• W2952100523 hasConceptScore W2952100523C2994168385 @default.
• W2952100523 hasConceptScore W2952100523C3019447875 @default.
• W2952100523 hasConceptScore W2952100523C43617362 @default.
• W2952100523 hasConceptScore W2952100523C55493867 @default.
• W2952100523 hasConceptScore W2952100523C71924100 @default.
• W2952100523 hasConceptScore W2952100523C86803240 @default.
• W2952100523 hasLocation W29521005231 @default.
• W2952100523 hasOpenAccess W2952100523 @default.
• W2952100523 hasPrimaryLocation W29521005231 @default.
• W2952100523 hasRelatedWork W1927254728 @default.
• W2952100523 hasRelatedWork W2022719705 @default.
• W2952100523 hasRelatedWork W2113912773 @default.
• W2952100523 hasRelatedWork W2126924389 @default.
• W2952100523 hasRelatedWork W2165188381 @default.
• W2952100523 hasRelatedWork W2261547780 @default.
• W2952100523 hasRelatedWork W2337873340 @default.
• W2952100523 hasRelatedWork W2846468914 @default.
• W2952100523 hasRelatedWork W2884026374 @default.
• W2952100523 hasRelatedWork W2888208674 @default.
• W2952100523 hasRelatedWork W2890424537 @default.
• W2952100523 hasRelatedWork W2903257335 @default.
• W2952100523 hasRelatedWork W2910808966 @default.
• W2952100523 hasRelatedWork W2951701336 @default.
• W2952100523 hasRelatedWork W2965498249 @default.
• W2952100523 hasRelatedWork W2984776303 @default.
• W2952100523 hasRelatedWork W2999037133 @default.
• W2952100523 hasRelatedWork W3003442873 @default.
• W2952100523 hasRelatedWork W3048677525 @default.
• W2952100523 hasRelatedWork W3200744244 @default.
• W2952100523 isParatext "false" @default.
• W2952100523 isRetracted "false" @default.
• W2952100523 magId "2952100523" @default.
• W2952100523 workType "dissertation" @default.