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

本文对与gramicidin S（GS）相关的5个线性五肽琥珀酰亚胺酯（-ONSu）进行环化，其中Val、Orn、Leu、D-Phe和Pro残基占据c端，Orn残基的δ氨基不受保护，研究Orn残基的δ氨基对环化的影响。h - d - ph - pro - valo - orn - leu - onsu在25‰（吡啶中肽的浓度：3 × 10^<-3> M）条件下环化得到半环单体GS和环二聚体GS，产率分别为15%和38%。另一方面，其他五肽onsu环化得到的主要是各活性酯c端氨基酸残基羧基与Orn残基δ氨基之间的酰胺键环五肽，而没有任何GS。从这些研究中发现，在不保护Orn残基的δ氨基的五肽- onsu环化过程中，特殊的序列是通过环二聚化直接合成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。h - d - ph - pro - d - tyrl - val - orn - leu - onsu与晶格的环化也得到了类似的结果。

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.