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

为了考察Orn残基上的增量氨基对环化反应的影响，对5种与甘草酸S(GS)有关的直链五肽琥珀酰亚胺酯(-ONSU)进行了环化反应，其中Val、Orn、Leu、D-Phe和Pro残基位于C-末端，Orn残基的增量-氨基不受保护。H-D-Phe-Pro-Val-Orn-Leu-ONSu在25ﾟC(吡啶中肽的浓度为3×10~(-3)~(-3)~gt；M)下在吡啶中环化生成半-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的环化反应主要生成环状五肽，涉及每个活性酯C端氨基酸残基的羧基和Orn残基的增量氨基之间的酰胺键，但没有生成任何量的GS。通过这些研究发现，在不保护Orn残基三角洲氨基的五肽环化反应中，特殊的序列是通过环二聚法直接合成GS所必需的，与用于天然GS生物合成的线性五肽前体(D-Phe-Pro-Val-Orn-Leu)是一致的。在与格雷辛有关的H-D-Phe-Pro-D-Tyr-Val-Orn-Leu-ONSu的环化反应研究中，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.