Self-condensation of a thiazole-peptide bearing a 21-membered loop into a library of giant macrocycles with multiple orthogonal loops.
[reaction: see text] Tetrapeptide analogue H-[Glu-Ser-Lys(Thz)]-OH, containing a turn-inducing thiazole constraint, was used as a template to produce a 21-membered structurally characterized loop by linking Glu and Lys side chains with a Val-Ile dipeptide. This template was oligomerized in one pot to a library (cyclo-[1](n)(), n = 2-10) of giant symmetrical macrocycles (up to 120-membered rings), fused to 2-10 appended loops that were carried intact through multiple oligomerization (chain extension) and cyclization (chain terminating) reactions of the template. A three-dimensional solution structure for cyclo-[1](3) shows all three appended loops projecting from the same face of the macrocycle. This is a promising approach to separating peptide motifs over large distances.
Singh
Yogendra
Y
Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia.
Hoang
Huy N
HN
Flanagan
Bernadine
B
Fairlie
David P
DP
D003500:Cyclization; D008968:Molecular Conformation; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry*
D010455:Peptides; D013844:Thiazoles