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Protein surface recognition by synthetic agents: Design and structural requirements of a family of artificial receptors that bind to cytochrome C
Author(s) -
Lin Qing,
Park Hyung Soon,
Hamuro Yoshitomo,
Lee Chang Sun,
Hamilton Andrew D.
Publication year - 1998
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(1998)47:4<285::aid-bip4>3.0.co;2-c
Subject(s) - chemistry , receptor , stereochemistry , cytochrome c , molecular recognition , cytochrome , lysine , protein design , hemeprotein , peptide , heme , binding site , hypervariable region , combinatorial chemistry , protein structure , biochemistry , molecule , enzyme , amino acid , organic chemistry , mitochondrion , gene
The design, synthesis, and evaluation of a novel series of receptors for protein surface recognition are described. The design of these agents is based around the attachment of four constrained peptide loops onto a central calix[4]arene scaffold. This arrangement mimics the role of the hypervariable loops in antibody combining regions and defines a large surface area for binding to a complementary region of the exterior of a target protein. Using affinity and gel filtration chromatographies we show that one particular receptor binds strongly to the surface of cytochrome c. The site of binding is presumably close to the heme edge region, which contains several charged lysine residues. This is supported by the observation that the receptor inhibits the reduction of Fe(III) cytochrome c to its Fe(II) form. We also show that binding is strongly dependent on the nature of the substituents on the lower rim of the calixarene. The nmr and computational studies suggest that this effect may be due to conformational differences among the differently substituted receptors. © 1998 John Wiley & Sons, Inc. Biopoly 47: 285–297, 1998