Direct synthesis of gramicidin S via cyclization of pentapeptide active-esters without protecting delta-amino group of Orn residue.

通过五肽活性酯环化直接合成短杆菌肽 S，无需保护 Orn 残基的 δ-氨基。

• 批准号: 02640428
• 负责人: TAMAKI Makoto
• 金额: $ 1.34万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02640428/
• 关键词: Gramicidin S; Direct synthesis; Cyclic dimerization; non protection; ペンタペプチド; 環化反応; オルニチン残基

Five linear pentapeptide succinimide esters (-ONSu) related to gramicidin S(GS), in which Val, Orn, Leu, D-Phe, and Pro residue occupys at C-terminal and delta-amino group of Orn residue is not protected, is cyclized in order to investigate an Influence of delta-amino group of Orn residue on the cyclization. The cyclization of H-D-Phe-Pro-Val-Orn-Leu-ONSu in pyridine at 25 ﾟC (concentration of peptide in pyridine : 3 x 10^<-3> M) produced semi-GS (cyclic monomer) and GS (cyclic dimer) in a yield of 15 and 38 %, respectively. On the other hand, the cyclization of other pentapeptide-ONSu gave mainly cyclic pentapeptides involving amide bond between the carboxyl group of amino acid residue at C-terminal of each active ester and the delta-amino group of Orn residue, but did not any amount of GS. From these studies, it was found that in the cyclization of pentapeptlde-ONSu without protecting delta-amino group of Orn residue, the special sequence is necessary to synthesize directly GS by the cyclic dimerization and is identical with the linear pentapeptide precusor(D-Phe-Pro-Val-Orn-Leu)used in the biosynthesis of natural GS. A simular result was obtained in the study of the cyclization of H-D-Phe-Pro-D-Tyr-Val-Orn-Leu-ONSu related to gratisn.

将与短杆菌肽S(GS)相关的五种线性五肽琥珀酰亚胺酯(-ONSu)环化，其中C端有Val、Orn、Leu、D-Phe和Pro残基，且Orn残基的δ氨基未被保护，以研究Orn残基的δ氨基对环化的影响。 H-D-Phe-Pro-Val-Orn-Leu-ONSu 在吡啶中于 25℃ 下环化（吡啶中肽的浓度：3 x 10^<-3> M）产生半 GS（环状单体）和 GS（环状二聚体），产率分别为 15 % 和 38 %。另一方面，其他五肽-ONSu的环化主要产生涉及各活性酯C端氨基酸残基的羧基与Orn残基的δ-氨基之间的酰胺键的环状五肽，但没有产生任何量的GS。这些研究发现，在不保护Orn残基δ-氨基的五肽-ONSu环化过程中，特殊序列是通过环状二聚直接合成GS所必需的，并且与天然GS生物合成中使用的线性五肽前体(D-Phe-Pro-Val-Orn-Leu)相同。在与gratisn相关的H-D-Phe-Pro-D-Tyr-Val-Orn-Leu-ONSu环化研究中也得到了类似的结果。