REACTIONS OF AMINES AND AMINO ACIDS WITH MALEIMIDES . STRUCTURE OF REACTION PRODUCTS DEDUCED FROM INFRARED AND NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
REACTIONS OF AMINES AND AMINO ACIDS WITH MALEIMIDES . STRUCTURE OF REACTION PRODUCTS DEDUCED FROM INFRARED AND NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
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DOI：
10.1021/bi00873a028
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发表时间：
1966-01-01
期刊：
影响因子：
2.9
通讯作者：
FLAVIN, M
中科院分区：
文献类型：
--
作者：
SHARPLES.NE;FLAVIN, M
人们已经认识到，N-乙基马来酰亚胺可以在相同的条件下与蛋白质中的氨基反应，这些条件通常用于烷基化巯基。然而，通过分离反应产物还没有明确地确定反应的性质。对马来酰亚胺与简单胺和氨基酸衍生物反应的研究是在这一考虑的推动下进行的，独立于发现马来酰亚胺可以在磷酸吡哆醛酶催化某些氨基酸的分解中与瞬时中间体反应。从马来酰亚胺与吡咯烷和哌啶反应，N-苯基马来酰亚胺与苯甲胺和甘草酰胺反应，N-乙基马来酰亚胺与哌啶、甘草酰胺和L-脯氨酸反应中分离得到产物。后一步反应生成的两个非对映异构体经电泳法分离，得到结晶苦味酸盐。这些化合物的红外和核磁共振光谱表明，在每种情况下，反应都涉及到马来酰亚胺双键上的氨基加成。在中性水溶液中，与氨基电离常数相近的伯基氨基酸相比，Pro的反应速度要快得多。此外，与含有伯氨基的氨基酸相比，在不同的条件下，Pro与马来酰亚胺的反应是可逆的，在固态、在强酸和可能在pH 5的溶液中加热可再生Pro。此外，还研究了马来酰亚胺与磷酸吡哆醛电子相关化合物之间电荷转移络合物的形成，结果为否定的。
It has been recognized that N-ethylmaleimide can react with amino groups in proteins under the same conditions which are often used to alkylate sulfhydryl groups. However, the nature of the reaction has not been unequivocally established by isolation of reaction products. An investigation of the reactions of maleimldes with simple amines and amino acid derivatives was prompted by this consideration, and independently by the discovery that maleimides can react with a transient intermediate in the decomposition of certain amino acids catalyzed by pyridoxal phosphate enzymes. Products were isolated from the reactions of maleimides with pyrrolidine and piperidine, of N-phenylmaleimide with benzylamine and glycylamide, and of N-ethylmaleimide with piperidine, glycylamide, and L-proline. The 2 diastereoisomers formed from L-proline in the latter reaction were separated by electrophoresis and isolated as crystalline picrates. Infrared and nuclear magnetic resonance spectroscopy of these compounds indicated that in every case the reaction involved addition of the amino group to the maleimide double bond. In neutral aqueous solution proline reacted much faster than primary amino acids with similar amino group ionization constants. Also, in contrast to amino acids containing the primary amino group, the reaction of proline with maleimides was reversible under various conditions, proline being regenerated by heating in the solid state, and in solution in strong acid, and probably also at pH 5. In addition, a search was made, with negative results, for charge-transfer complex formation between maleimldes and compounds electronically related to pyridoxal phosphate.