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Miniature protein ligands for protei...
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Rutledge, Stacey Erin.
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Miniature protein ligands for protein surfaces.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Miniature protein ligands for protein surfaces./
作者:
Rutledge, Stacey Erin.
面頁冊數:
349 p.
附註:
Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4822.
Contained By:
Dissertation Abstracts International64-10B.
標題:
Biophysics, General. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109456
ISBN:
0496569984
Miniature protein ligands for protein surfaces.
Rutledge, Stacey Erin.
Miniature protein ligands for protein surfaces.
- 349 p.
Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4822.
Thesis (Ph.D.)--Yale University, 2003.
This dissertation describes the design, molecular evolution and characterization of miniature protein ligands for protein surfaces, identified through a strategy known as protein grafting. In protein grafting, an alpha-helical functional epitope is transferred to and stabilized on the helical scaffold provided by the small yet stable protein avian pancreatic polypeptide (aPP) to yield highly functional miniature proteins. Chapter 1 explores the utility of protein grafting for the identification of miniature protein ligands for shallow protein grooves, which represent challenging targets for molecular recognition. Protein grafting in combination with molecular evolution by phage display was applied to the recognition of a shallow protein-binding groove on the surface of the KIX domain of the coactivator CBP, resulting in the identification of phosphorylated peptide ligands which possess nanomolar affinity and high specificity for CBP KIX. Furthermore, this strategy identified peptide ligands capable of high affinity and specific recognition of CBP KIX even in the absence of phosphorylation. Chapter 2 describes progress towards the identification of miniature proteins which exhibit significant homolog specificity, or the ability to discriminate among closely related protein surfaces. Specifically, the ability of the three previously described PPBH3 miniature protein ligands to discriminate between the closely related anti-apoptotic proteins Bcl-2 and Bcl-XL was investigated; the three PPBH3 peptides were found to possess comparable levels of homolog specificity. Based on known structural differences between the BH3-binding grooves of Bcl-2 and Bcl-XL, a library of PPBH3 variants was generated which was designed to aid in the identification of miniature proteins which exhibit enhanced homolog specificity for either Bcl-2 or Bcl-X L.
ISBN: 0496569984Subjects--Topical Terms:
1019105
Biophysics, General.
Miniature protein ligands for protein surfaces.
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This dissertation describes the design, molecular evolution and characterization of miniature protein ligands for protein surfaces, identified through a strategy known as protein grafting. In protein grafting, an alpha-helical functional epitope is transferred to and stabilized on the helical scaffold provided by the small yet stable protein avian pancreatic polypeptide (aPP) to yield highly functional miniature proteins. Chapter 1 explores the utility of protein grafting for the identification of miniature protein ligands for shallow protein grooves, which represent challenging targets for molecular recognition. Protein grafting in combination with molecular evolution by phage display was applied to the recognition of a shallow protein-binding groove on the surface of the KIX domain of the coactivator CBP, resulting in the identification of phosphorylated peptide ligands which possess nanomolar affinity and high specificity for CBP KIX. Furthermore, this strategy identified peptide ligands capable of high affinity and specific recognition of CBP KIX even in the absence of phosphorylation. Chapter 2 describes progress towards the identification of miniature proteins which exhibit significant homolog specificity, or the ability to discriminate among closely related protein surfaces. Specifically, the ability of the three previously described PPBH3 miniature protein ligands to discriminate between the closely related anti-apoptotic proteins Bcl-2 and Bcl-XL was investigated; the three PPBH3 peptides were found to possess comparable levels of homolog specificity. Based on known structural differences between the BH3-binding grooves of Bcl-2 and Bcl-XL, a library of PPBH3 variants was generated which was designed to aid in the identification of miniature proteins which exhibit enhanced homolog specificity for either Bcl-2 or Bcl-X L.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3109456
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