Structural mimicry of two cytochrome b(562) interhelical loops using macrocycles constrained by oxazoles and thiazoles.
A major chemical challenge is the structural mimicry of discontinuous protein surfaces brought into close proximity through polypeptide folding. We report the design, synthesis, and solution structure of a highly functionalized saddle-shaped macrocyclic scaffold, constrained by oxazoles and thiazoles, supporting two short peptide loops projecting orthogonally from the same face of the scaffold. This structural mimetic of two interhelical loops of cytochrome b(562) illustrates a promising approach to structurally mimicking discontinuous loops of proteins.
Singh
Yogendra
Y
Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.
Stoermer
Martin J
MJ
Lucke
Andrew J
AJ
Guthrie
Tom
T
Fairlie
David P
DP
D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D003573:Cytochrome b Group / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010080:Oxazoles / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D012996:Solutions; D013499:Surface Properties; D013844:Thiazoles / Q000737:chemistry*
D003573:Cytochrome b Group; D029968:Escherichia coli Proteins; D047028:Macrocyclic Compounds; D010080:Oxazoles; D012996:Solutions; D013844:Thiazoles; C017850:cytochrome b562, E coli