Department of Applied Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohamashi, Japan.
Orig Life Evol Biosph. 2011 Oct;41(5):413-35. doi: 10.1007/s11084-011-9240-7. Epub 2011 May 12.
A good comprehension of the reactivity of peptides in aqueous solution is fundamental in prebiotic chemistry, namely for understanding their stability and behavior in primitive oceans. Relying on the stereoselectivity of the involved reactions, there is a huge interest in amino acid derivatives for explaining the spontaneous emergence of homochirality on primitive Earth. The corresponding kinetic and thermodynamic parameters are however still poorly known in the literature. We studied the reactivity of alanylalanine in acidic to neutral conditions as a model system. The hydrolysis into amino acids, the epimerization of the N-terminal residue, and the cyclization into diketopiperazine could be successfully identified and studied. This kinetic investigation highlighted interesting behaviors. Complex mechanisms were observed in very acidic conditions. The relative kinetic stability of the diastereoisomers of the dipeptide is highly dependent of the pH, with the possibility to dynamically destabilize the thermodynamically more stable diastereoisomers. The existence of the cyclization of dipeptides adds complexity to the system. On one hand it brings additional stereoselectivities; on the other hand fast racemization of heterochiral dipeptides is obtained.
在原始海洋中理解肽在水溶液中的反应性对于前生物化学来说至关重要，特别是对于理解它们的稳定性和行为。由于涉及的反应具有立体选择性，因此人们对氨基酸衍生物非常感兴趣，希望用其解释原始地球上手性的自发出现。然而，文献中仍然很少了解相应的动力学和热力学参数。我们以丙氨酰丙氨酸为模型体系，研究了其在酸性至中性条件下的反应性。成功地鉴定并研究了其水解成氨基酸、N-末端残基的差向异构化以及环化生成二酮哌嗪的反应。这项动力学研究揭示了有趣的行为。在非常酸性的条件下观察到了复杂的机制。二肽的非对映异构体的相对动力学稳定性高度依赖于 pH 值，这使得热力学上更稳定的非对映异构体有可能动态失稳。二肽的环化增加了体系的复杂性。一方面，它带来了额外的立体选择性；另一方面，得到了异手性二肽的快速外消旋化。
