Engineering the structure of an N-terminal β-turn to maximize screw-sense preference in achiral helical peptide chains.
Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 310 helical conformations in which enantiomeric left- and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a right-handed screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.
School of Chemistry, University of Manchester , Oxford Road, Manchester M13 9PL, U.K.
Matteo
M
De Poli
Liam
L
Byrne
Robert A
RA
Brown
Jordi
J
Solà
Alejandro
A
Castellanos
Thomas
T
Boddaert
Romina
R
Wechsel
Jonathan D
JD
Beadle
Jonathan
J
Clayden
D000596:Amino Acids / Q000737:chemistry*; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D002219:Carbamates / Q000737:chemistry*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D002219:Carbamates; D009842:Oligopeptides; D010455:Peptides; C100049:2-aminoisobutyric acid; D014633:Valine