Alferiev I S, Hinson J T, Ogle M, Breuer E, Levy R J
Children's Hospital of Philadelphia, Division of Cardiology, Abramson Research Center, PA 19104-4318, USA.
Biomaterials. 2001 Sep;22(18):2501-6. doi: 10.1016/s0142-9612(00)00440-3.
Epoxy crosslinking agents have been investigated for use in the fabrication of bioprosthetic devices, such as heterograft heart valve prostheses. It has been generally assumed that epoxy crosslinking takes place via amino-epoxy reactions. The present study investigated the hypothesis that the reactions of methionine residues with epoxides also can occur in biomaterial crosslinking. A series of model reactions were studied in which a mono-epoxide was combined with individual alkyl sulfides. In the present studies epoxides rapidly alkylate aliphatic sulfides, including methionine derivatives, in buffered aqueous solutions at room temperature and pH close to neutral, forming sulfonium compounds, which are stable at pH 5-7 at temperatures up to 50 degrees C, except for cases in which methionine derivatives with non-protected carboxy groups are used. The rate of reaction remains practically unchanged within the range of pH from 5 to 12, whereas in strongly alkaline media the reverse reaction occurs. This discovery can provide a better understanding of processes occurring in the fixation of bioprosthetic tissues with polyepoxides. It can also develop into a site-specific method to label methionine residues in proteins. The carboxy group-containing sulfonium betaines derived from N-protected methionines undergo cyclization in unexpectedly mild conditions, which can be used as an efficient method for preparation of N-protected 2-amino-4-butyrolactones with sensitive protective groups.
人们已经对环氧交联剂用于制造生物假体装置（如异种移植心脏瓣膜假体）进行了研究。一般认为环氧交联是通过氨基 - 环氧反应发生的。本研究调查了一个假设，即甲硫氨酸残基与环氧化物的反应在生物材料交联中也可能发生。研究了一系列模型反应，其中将单环氧化物与各个烷基硫化物混合。在本研究中，环氧化物在室温及接近中性的pH值的缓冲水溶液中能迅速使包括甲硫氨酸衍生物在内的脂肪族硫化物烷基化，形成锍化合物，除了使用带有未保护羧基的甲硫氨酸衍生物的情况外，这些锍化合物在pH值为5 - 7、温度高达50摄氏度时是稳定的。在pH值从5到12的范围内，反应速率实际上保持不变，而在强碱性介质中会发生逆反应。这一发现有助于更好地理解用聚环氧化物固定生物假体组织时发生的过程。它还可以发展成为一种标记蛋白质中甲硫氨酸残基的位点特异性方法。由N - 保护的甲硫氨酸衍生的含羧基的锍甜菜碱在出乎意料的温和条件下发生环化，这可以用作制备带有敏感保护基团的N - 保护的2 - 氨基 - 4 - 丁内酯的有效方法。
