Chiral alpha-aminoxy acid/achiral cyclopropane alpha-aminoxy acid unit as a building block for constructing the alpha N-O helix.
The monomer 1 derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides 2-9 consisting of a chiral alpha-aminoxy acid and an achiral alpha-aminoxy acid such as OAcc were synthesized and their structures characterized. The eight-membered-ring intramolecular hydrogen bond, namely the alpha N-O turn, was formed between adjacent residues independent of their chirality. However, the helix formation was sequence-dependent. Dipeptide 2 bearing chiral alpha-aminoxy acid (d-OAA) at the N-terminus and achiral OAcc at the C-terminus preferentially adopted a right-handed 1.8(8) helical structure, but dipeptide 3 (OAcc-d-OAA) did not. Theoretical calculation results, in good agreement with experimental ones, revealed that the biased handedness of alpha N-O turn found in OAcc residue depends on its preceding chiral residue. It was then found that the helical conformation was destroyed in the case of oligopeptides 6 and 7 [OAA-(OAcc)(n), n = 2, 3]. The crystal structure of tripeptide 8 ((i)PrCO-d-OVal-OAcc-d-OVal-NH(i)Bu) further disclosed the helical structure formed by three consecutive homochiral alpha N-O turns. This study has uncovered achiral aminoxy acid residues such as the OAcc unit as a useful building block to be incorporated into chiral aminoxy peptides to mimic chiral helix structure.
Yang
Dan
D
Department of Chemistry, Fudan University, Shanghai 200433, China. yangdan@hku.hk
Chang
Xiao-Wei
XW
Zhang
Dan-Wei
DW
Jiang
Ze-Feng
ZF
Song
Ke-Sheng
KS
Zhang
Yu-Hui
YH
Zhu
Nian-Yong
NY
Weng
Lin-Hong
LH
Chen
Min-Qin
MQ
D000596:Amino Acids / Q000737:chemistry*; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry*
D000596:Amino Acids; D003521:Cyclopropanes; D004151:Dipeptides; D009842:Oligopeptides; C015766:cyclopropanecarboxylic acid; D009584:Nitrogen; D010100:Oxygen