Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Reversible Sulfur Reactions in Pre-Equilibrated and Catalytic Self-Screening Dynamic Combinatorial Chemistry Protocols
KTH, Skolan för kemivetenskap (CHE), Kemi.
2006 (Engelska)Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Dynamic Combinatorial Chemistry (DCC) is a recently introduced supramolecular approach to generate dynamically interchanging libraries of compounds. These libraries are made of different building blocks that reversibly interact with one another and spontaneously assemble to encompass all possible combinations. If a target molecule, for instance a receptor is added to the system and one or more molecules show affinity to the target species, these compounds will, according to Le Châtelier´s principle, be amplified on the expense of the other non-bonding constituents. To date, only a handful of different systems and formats have been used. Hence, to further advance the technique, especially when biological systems are targeted, new reaction types and new screening methods are necessary. This thesis describes the development of reversible sulfur reactions, thiol/disulfide interchange and transthiolesterification (the latter being a new reaction type for DCC), as means of generating reversible covalent bond reactions. Two different types of target proteins are used, enzymes belonging to the hydrolase family and the plant lectin Concanavalin A. Furthermore, two new screening/analysis methods not previously used in DCC are also presented; the quartz crystal microbalance (QCM)-technique and catalytic self-screening.

Ort, förlag, år, upplaga, sidor
Stockholm: KTH , 2006. , s. 44
Serie
Trita-IOK, ISSN 1100-7974 ; 2006:102
Nyckelord [en]
Dynamic Combinatorial Chemistry, Reversible sulfur reactions, Catalytic self-screening, Carbohydrates, Lectins, Quartz Crystal Microbalance
Nationell ämneskategori
Organisk kemi
Identifikatorer
URN: urn:nbn:se:kth:diva-3917ISBN: 91-7178-323-7 (tryckt)OAI: oai:DiVA.org:kth-3917DiVA, id: diva2:10008
Presentation
2006-05-02, F3, Lindstedtsvägen 26, KTH, Stockholm, 10:00
Anmärkning
QC 20101118Tillgänglig från: 2006-04-10 Skapad: 2006-04-10 Senast uppdaterad: 2010-11-18Bibliografiskt granskad
Delarbeten
1. Catalytic Self-Screening of Cholinesterase Substrates from a Dynamic Combinatorial Thioester Library
Öppna denna publikation i ny flik eller fönster >>Catalytic Self-Screening of Cholinesterase Substrates from a Dynamic Combinatorial Thioester Library
2004 (Engelska)Ingår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 43, nr 28, s. 3716-3718Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Simply the best: Dynamic combinatorial chemistry coupled to enzyme catalysis was used to identify enzyme substrates in a library constructed from a series of thioesters and thiols by transesterification. The library was directly coupled to the catalytic action of acetylcholinesterase, which selectively hydrolyzed the best substrate candidates (see schematic representation). The process allowed rapid identification of discrete substrates.

Nyckelord
combinatorial chemistry; enzyme catalysis hydrolysis; proteomics; transesterification
Nationell ämneskategori
Organisk kemi
Identifikatorer
urn:nbn:se:kth:diva-8265 (URN)10.1002/anie.200454165 (DOI)000222793600019 ()15248281 (PubMedID)2-s2.0-4544244707 (Scopus ID)
Anmärkning
QC 20100818Tillgänglig från: 2008-04-25 Skapad: 2008-04-25 Senast uppdaterad: 2020-03-09Bibliografiskt granskad
2. Dynamic Combinatorial Thiolester Libraries for Efficient Catalytic Self-Screening of Hydrolase Substrates
Öppna denna publikation i ny flik eller fönster >>Dynamic Combinatorial Thiolester Libraries for Efficient Catalytic Self-Screening of Hydrolase Substrates
2006 (Engelska)Ingår i: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, nr 1, s. 285-291Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Dynamic combinatorial thiolester libraries were efficiently generated from pools of thiols and acyl functionalities through reversible transthiolesterification in aqueous media at neutral pH. The dynamic features of the library generation were investigated, and the libraries were screened against acetylcholinesterase, clearly demonstrating the catalytic self-screening of its substrates from the constituents. Acetyl- and propionylthiocholine were easily identified as the best substrates for the enzyme, whereas other constituents showed lower efficiency or were inactive. A range of hydrolases was furthermore screened for rapid substrate identification, clearly demonstrating the differences in selectivity. The results show that transthiolesterification is a useful method to generate dynamic libraries, and that the catalytic self -screening concept is highly valuable for substrate identification.

Nyckelord
combinatorial chemistry; enzyrne catalysis; hydrolysis; transesterification
Nationell ämneskategori
Organisk kemi
Identifikatorer
urn:nbn:se:kth:diva-8266 (URN)10.1002/ejoc.200500699 (DOI)000234237500028 ()2-s2.0-33745819380 (Scopus ID)
Anmärkning
QC 20100818Tillgänglig från: 2008-04-25 Skapad: 2008-04-25 Senast uppdaterad: 2019-12-20Bibliografiskt granskad
3. Quartz crystal microbalance bioaffinity sensor for rapid identification of glycosyldisulfide lectin inhibitors from a dynamic combinatorial library
Öppna denna publikation i ny flik eller fönster >>Quartz crystal microbalance bioaffinity sensor for rapid identification of glycosyldisulfide lectin inhibitors from a dynamic combinatorial library
Visa övriga...
2006 (Engelska)Ingår i: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 22, nr 1, s. 42-48Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Carbohydrate-lectin,interactions were probed with dynamic combinatorial libraries, using the plant lectin Concanavalin A as target species. The dynamic combinatorial libraries were generated from a pool of thiol components through reversible thiol-disulfide interchange, and screened using a simple and efficient method based on a quartz crystal microbalance setup. It was found that dimers based on 1-thio- and 6-thin-mannose analogues were the most active inhibitors. Furthermore, the results clearly show that the 6-thio-mannose possess unique characteristics compared to its oxygen-containing counterpart.

Nyckelord
quartz crystal microbalance; dynamic combinatorial chemistry; glycochemistry; carbohydrates; lectins; molecular recognition
Nationell ämneskategori
Organisk kemi
Identifikatorer
urn:nbn:se:kth:diva-8269 (URN)10.1016/j.bios.2005.11.024 (DOI)000241040600006 ()16406568 (PubMedID)2-s2.0-33746607715 (Scopus ID)
Anmärkning
QC 20100818Tillgänglig från: 2008-04-25 Skapad: 2008-04-25 Senast uppdaterad: 2020-03-09Bibliografiskt granskad

Open Access i DiVA

fulltext(969 kB)1522 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 969 kBChecksumma MD5
ccde61e724b18463b346f2d25aa13f9321614b00380c3f768186350ff72891910443ccf0
Typ fulltextMimetyp application/pdf

Sök vidare i DiVA

Av författaren/redaktören
Larsson, Rikard
Av organisationen
Kemi
Organisk kemi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 1522 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 762 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf