Arginase (EC 3.5.3.1) is the bimanganese enzyme that converts L‐arginine into ornithine and urea. This enzyme was discovered more than a century ago and early α‐amino acids were identified as weak inhibitors. It was only during the 90s, after nitric oxide (NO) was reported as one of the most important biological mediators and when tight interrelation of arginase and NO synthase was found, that the development of arginase inhibitors was accelerated. The regulation of arginase activity by the N‐hydroxy‐L‐arginine (3, NOHA) intermediate of the NO synthesis was the starting point of the N‐hydroxy‐nor‐arginine (21, nor‐NOHA) that proved to be the first micromolar inhibitor. The previously known manganese and arginase binding by borate inspired the 2(S)‐amino‐6‐boronohexanoic acid (39, ABH) and S‐(2‐boronoethyl)‐L‐cysteine (40, BEC) now both considered as reference compounds in arginase inhibition. The high‐resolution crystal structure of arginase and molecular modeling has rendered possible the recent design of (53) the strongest α,α‐disubstituted derivatives of ABH. Simultaneously, traditional medicinal plants have contributed as a source of molecular diversity to the discovery of arginase inhibitors. This rational, step‐by‐step approach serves as guide in the present review where emphasis is placed on structure activity relationships.

中文翻译：

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精氨酸酶抑制剂：一个世纪以来的合理方法

精氨酸酶（EC 3.5.3.1）是将L-精氨酸转化为鸟氨酸和尿素的双锰酶。这种酶在一个多世纪前就被发现，早期的α-氨基酸被认为是弱抑制剂。直到90年代，一氧化氮（NO）被报道为最重要的生物介质之一，并且当发现精氨酸酶和NO合酶紧密相关时，精氨酸酶抑制剂的发展才得以加速。NO合成的N-羟基-L-精氨酸（3，NOHA）中间体对精氨酸酶活性的调节是N-羟基-去甲精氨酸（21，nor-NOHA）的起点微摩尔抑制剂。硼酸对锰和精氨酸酶的先前结合作用激发了2（S）氨基-6-硼己酸（39，ABH）和S-（2-硼乙基）-L-半胱氨酸（40，BEC）现在都被认为是精氨酸酶抑制作用的参考化合物。精氨酸酶的高分辨率晶体结构和分子建模使（53）ABH最强的α，α-二取代衍生物的最新设计成为可能。同时，传统的药用植物为精氨酸酶抑制剂的发现提供了分子多样性的来源。这种合理的，循序渐进的方法在当前的审查中作为指南，重点放在结构活动关系上。