Replacement of the α-hydrogen atom of
L-α-amino acids with an alkyl substituent results in α,α-disubstituted amino acids. The modification changes the properties of the amino acids. Incorporation of α,α-disubstituted amino acids into oligopeptides restricts the conformational freedom of their peptides. The author developed a synthetic route for optically active α-ethylated α,α-disubstituted amino acids using chiral cyclic 1,2-diol, and disclosed that the preferred conformation of peptides composed of chiral α-ethylated disubstituted amino acids is a fully planar conformation, whereas that of chiral α-methylated disubstituted amino acids is a 3
10-helical structure. Furthermore, the author designed and synthesized two chiral cyclic α,α-disubstituted amino acids,
i.e., (3
S,4
S)-1-amino-3,4-di(methoxy)cyclopentanecarboxylic acid {(
S,
S)-Ac
5c
dOM}, and (1
R,6
R)-8-aminobicyclo-[4.3.0]non-3-ene-8-carboxylic acid {(
R,
R)-Ab
5,6=c}. They do not have a chiral center at the α-position, but do have chiral centers on the side-chain cyclopentane or the bicyclic skeleton. The preferred secondary structure of the (
S,
S)-Ac
5c
dOM homopeptides was the left-handed (
M) 3
10-helical structure (hexapeptide) and the left-handed (
M) α-helical structure (octa- and decapeptides), while that of the (
R,
R)-Ab
5,6=c hexapeptide was both the right-handed (
P) and left-handed (
M) 3
10-helices. These results indicate that the side-chain chiral centers affect the secondary structure of their peptides, and the side-chain chiral environment is important for the control of the helical-screw direction of peptides.
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