Conformational studies on peptides containing α,α-disubstituted α-amino acids: chiral cyclic α,α-disubstituted α-amino acid as an α-helical inducer
Conformational studies on peptides containing α,α-disubstituted α-amino acids: chiral cyclic α,α-disubstituted α-amino acid as an α-helical inducer
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DOI：
10.1039/c0ob01146k
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Tanaka, Masakazu
中科院分区：
文献类型：
--
作者：
Demizu, Yosuke;Doi, Mitsunobu;Tanaka, Masakazu
将4种α，α-二取代氨基酸[α-氨基异丁酸、1-氨基环戊烷羧酸(Ac(5)c)、(3S，4S)-1-amino-(3，4-dimethoxy)cyclopentanecarboxylic酸[(S，S)-Ac(5)c(DOM)]及其对映体(R，R)-Ac(5)c(DOM)引入L亮氨酸六肽和非亮氨酸六肽中。Cbz-(L-亮氨酸-L-亮氨酸-亮氨酸-DAA)(2)-OMe[DAA=1：aib；2：Ac(5)c；3：(S，S)-Ac(5)c(DOM)；4：(R，R)-Ac(5)c(DOM)]和Boc-(L-Leu-L-Leu-DAA)(3)-OMe[DAA=5：Aib；6：Ac(5)c；7：(S，S)-Ac(5)c(DOM)；8：(R，R)-Ac(5)c(DOM)]，通过红外光谱、圆二色谱和X-射线单晶分析对其进行了表征。圆二色谱表明，AIB六肽1和Ac(5)c六肽2形成右旋(P)3(10)螺旋，而Ac(5)c(DOM)六肽3和4形成(P)3(10)和α螺旋的混合物。AIB九肽5形成(P)3(10)螺旋，ac(5)c九肽6形成(P)3(10)和α螺旋的混合物，ac(5)c(DOM)九肽7和8形成(P)α螺旋。X-射线晶体分析表明，AIB六肽1形成了(P)3(10)螺旋，而(S，S)-Ac(5)c(DOM)六肽3形成了(P)α螺旋。此外，(R，R)-Ac(5)-c(DOM)-Ac(5)-C-(DOM)还形成(P)-α-螺旋。AIB和非手性Ac(5)c残基有在短肽中形成3(10)螺旋的倾向，而手性Ac(5)c(Dom)残基有形成α螺旋的倾向。
Four types of alpha,alpha-disubstituted amino acids {i.e., alpha-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Ac(5)c), (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)] and its enantiomer (R,R)-Ac(5)c(dOM)} were introduced into L-leucine-based hexapeptides and nonapeptides. The dominant conformations of eight peptides: Cbz-(L-Leu-L-Leu-dAA)(2)-OMe [dAA = 1: Aib; 2: Ac(5)c; 3: (S, S)-Ac(5)c(dOM); 4: (R, R)-Ac(5)c(dOM)] and Boc-(L-Leu-L-Leu-dAA)(3)-OMe [dAA = 5: Aib; 6: Ac(5)c; 7: (S, S)-Ac(5)c(dOM); 8: (R, R)-Ac(5)c(dOM)], were investigated by IR, CD spectra and X-ray crystallographic analysis. The CD spectra revealed that Aib hexapeptide 1 and Ac(5)c hexapeptide 2 formed right-handed (P) 3(10)-helices, while Ac(5)c(dOM) hexapeptides 3 and 4 formed a mixture of (P) 3(10)- and alpha-helices. The Aib nonapeptide 5 formed a (P) 3(10)-helix, the Ac(5)c nonapeptide 6 formed a mixture of (P) 3(10)- and alpha-helices, and the Ac(5)c(dOM) nonapeptides 7 and 8 formed (P) alpha-helices. X-Ray crystallographic analysis revealed that the Aib hexapeptide 1 formed a (P) 3(10)-helix, while (S, S)-Ac(5)c(dOM) hexapeptide 3 formed a (P) alpha-helix. In addition, the Ac(5)c nonapeptide 6 and (R, R)-Ac(5)c(dOM) nonapeptide 8 formed (P) alpha-helices. The Aib and achiral Ac(5)c residues have the propensity to form 3(10)-helices in short peptides, whereas the chiral Ac(5)c(dOM) residues have a penchant for forming alpha-helices.