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A mixed-alpha,beta miniprotein stereochemically reprogrammed to high-binding affinity for acetylcholine

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Title A mixed-alpha,beta miniprotein stereochemically reprogrammed to high-binding affinity for acetylcholine
 
Creator RANA, S
KUNDU, B
DURANI, S
 
Subject cation-pi interactions
designed beta-hairpin
protein secondary structure
alpha-helical peptides
aromatic interactions
successive residues
molecular-dynamics
circular-dichroism
globular-proteins
noe spectroscopy
protein design
stereochemical programming
molecular recognition
peptidomimetics
pi-pi interaction
cation-pi interaction
 
Description The protein-structure space is limited to L configuration in the asymmetric alpha-amino acid structures, the function space, on other hand, seems limitless because of the chemical diversity in the amino acid side chain structures. The chemical diversity in side chain structure may be multiplied beneficially with the stereochemical diversity in main chain structure; thus, de novo protein design may be explored for customizing molecular structures stereochemically and molecular functions chemically. Illustrating de novo design in the structure space Of L and D alphabet, canonical all-P folds Of poly-L structure were reprogrammed as bracelet, boat, and canoe-shaped molecules-the "boat" as a receptor-like pocket and the "canoe" as a metal-ion receptor-simply by mutating specific L-amino acid residues to the corresponding D stereochemical structure. Demonstrating customization Of molecular shape stereochemically and function chemically, a 15-residue mixed-alpha, beta miniprotein Of canonical Poly-L structure is now reprogrammed stereochemically as a cup-shaped receptor for acetylcholine via cation-Tu interaction with a triad of aromatic side chains placed in mimicry of the acetylcholine-receptor sites both natural and artificial. Evidence from CD, fluorescence, NMR, DSC, ITC, MD, and molecular-docking studies is presented to show that a rationally designed 15-residue mixed-L, D peptide is a cooperatively ordered molecular fold in the stereochemically specified molecular morphology, submicromolar in affinity of acetylcholine and thus an acetylcholine receptor exceptionally small and simple. (c) 2007 Wiley Periodicals.
 
Publisher JOHN WILEY & SONS INC
 
Date 2011-08-04T09:48:19Z
2011-12-26T12:54:39Z
2011-12-27T05:42:49Z
2011-08-04T09:48:19Z
2011-12-26T12:54:39Z
2011-12-27T05:42:49Z
2007
 
Type Article
 
Identifier BIOPOLYMERS, 87(4), 231-243
0006-3525
http://dx.doi.org/10.1002/bip.20829
http://dspace.library.iitb.ac.in/xmlui/handle/10054/9319
http://hdl.handle.net/10054/9319
 
Language en