Comparison of conformation and antimicrobial activity of synthetic analogs of gramicidin S: Stereochemical consideration of the role of D‐phenylalanine in the antibiotic
Comparison of conformation and antimicrobial activity of synthetic analogs of gramicidin S: Stereochemical consideration of the role of D‐phenylalanine in the antibiotic
复制标题
短杆菌肽S合成类似物的构象和抗菌活性比较：D-苯丙氨酸在抗生素中作用的立体化学考虑
DOI：
10.1002/bip.1978.360170613
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发表时间：
1978
期刊：
影响因子：
2.9
通讯作者：
U. Nagai
中科院分区：
文献类型：
--
作者：
M. Kawai;U. Nagai
为了研究D-氨基酸残基在保持β-SHAP构象稳定中的作用以及在革兰菌素S(GS)抗菌活性中的作用，合成了D-丙氨酸、L-丙氨酸、甘氨酸和α-氨基异丁酸取代D-Phe的四个GS类似物。含D-丙氨酸和甘氨酸的类似物显示出抗菌活性，而含有L-丙氨酸和AIB的类似物则没有抑菌活性。通过ORD和CD光谱的比较和选择性甲基化方法研究了这些类似物及其衍生物的构象。结果表明，生物活性类似物具有β-Sheet构象，而非活性类似物具有与GS不同的构象。这表明D-丙氨酸-Pro和甘氨酸-Pro序列倾向于β-弯曲型，而L-丙氨酸-Pro和AIb-Pro序列并非如此，因为LaA和AIb残基上α-碳原子上L侧甲基的存在破坏了β-弯曲型。这就解释了为什么非活性类似物具有与活性类似物不同的构象，从而导致活性丧失。
In order to study the role of D‐amino acid residues in keeping the stable β‐sheet conformation and in the antimicrobial activity of gramicidin S (GS), the four analogs of GS containing D‐Ala, L‐Ala, Gly, and Aib (α‐aminoisobutyric acid) in place of D‐Phe were synthesized. D‐Ala‐and Gly‐containing analogs showed antimicrobial activity, while those containing L‐Ala and Aib showed no activity. Conformation of these analogs and their derivatives were studied by comparison of ORD and CD spectra and by slective methylation method. It is concluded that the biologically active analogs have β‐sheet conformation while inactive analogs have a much different conformation from that of GS. This indicates that D‐Ala‐Pro and Gly‐Pro sequences favor taking a β‐bend form but L‐Ala‐Pro and Aib‐Pro sequences do not because the presence of L‐side methyl group on the α‐carbon atom of LAla and Aib residues destabilizes the β‐bend form. This would explain why the inactive analogs which take a different conformation from that of the active ones result in the loss of activity.