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Applications of Combinatorial Librar...

McGee, Christopher James.

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Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags./
Author:	McGee, Christopher James.
Description:	333 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-03, Section: B, page: 1471.
Contained By:	Dissertation Abstracts International72-03B.
Subject:	Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3434799
ISBN:	9781124420684

Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags.
McGee, Christopher James.

Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags. - 333 p.

Source: Dissertation Abstracts International, Volume: 72-03, Section: B, page: 1471.

Thesis (Ph.D.)--University of California, Irvine, 2010.

The ability to image biochemical and phenotypical changes at the molecular level is imperative for the investigation and understanding of the molecular mechanisms that govern health and disease. Since 1962, the green fluorescent protein (GFP) has been the tool of choice for imaging tens of thousands of otherwise invisible proteins. Despite its role as one of the most important tools in contemporary bioscience, the sheer size of GFP (238 amino acids) can limit its applications. The labeling of shorter genetically expressed peptide tags (&sim;10 amino acids) with fluorogenic small molecules has emerged as a promising alternative.

ISBN: 9781124420684Subjects--Topical Terms:

518028
Biochemistry.

Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags.
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100 1 $a McGee, Christopher James. $3 3187469
245 1 0 $a Applications of Combinatorial Libraries To The Discovery of Chemically Reactive Peptide Tags.
300 $a 333 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-03, Section: B, page: 1471.
500 $a Adviser: David L. Van Vranken.
502 $a Thesis (Ph.D.)--University of California, Irvine, 2010.
520 $a The ability to image biochemical and phenotypical changes at the molecular level is imperative for the investigation and understanding of the molecular mechanisms that govern health and disease. Since 1962, the green fluorescent protein (GFP) has been the tool of choice for imaging tens of thousands of otherwise invisible proteins. Despite its role as one of the most important tools in contemporary bioscience, the sheer size of GFP (238 amino acids) can limit its applications. The labeling of shorter genetically expressed peptide tags (&sim;10 amino acids) with fluorogenic small molecules has emerged as a promising alternative.
520 $a This trend has prompted our group to screen millions of peptides from combinatorial one-bead one-compound (OBOC) libraries. In our case, these libraries contain 130 mM TentaGel beads each bearing &sim;300 pmol of an unknown peptide. These libraries can be reacted with a fluorogenic small molecule and any peptide reacting with the molecule will cause the bead to fluoresce (termed a "hit"). Isolation of the bead hits allows the peptide to be sequenced, and further evaluated for use in protein visualization.
520 $a Our advances in synthesis and sequencing methodology has expanded the power of OBOC libraries to include short cysteine-rich peptides for applications such as biarsenical binding tags, metal-chelating species, and cysteine-rich pharmaceuticals. Our screens of cysteine-rich peptides have led to the discovery of several new reactive biarsenical motifs. Certainly these motifs serve to identify endogenous proteins targets. And, with optimization, could serve as better tags for fluorescent labeling in living cells.
520 $a We have also identified the first peptide tags that react selectively with 1,4-dicarbonyls to give fluorescent isoindoles. Currently, the biarsenical-tetracysteine system is state of the art for labeling living cells, but hinges non-covalent bonding to cytotoxic arsenic. These peptide tags that react selectively and covalently with 3-benzoyl-2-quinolinecarboxaldehyde (BQCA) represent progress towards the betterment of protein labeling, and ultimately, an understanding of the macromolecules that define us.
590 $a School code: 0030.
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650 4 $a Cellular biology. $3 3172791
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710 2 $a University of California, Irvine. $b Chemistry - Ph.D.. $3 2094938
773 0 $t Dissertation Abstracts International $g 72-03B.
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791 $a Ph.D.
792 $a 2010
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3434799