Session: Current Topics in Biological Chemistry:

2,5-diketopiperazines (DKPs) are cyclic dipeptides ubiquitously found in nature. In particular, cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) are frequently detected in many microbial cultures. Each of these DKPs has four possible stereoisomers due to the presence of two chirality centers. Yet, absolute configurations of natural DKPs are often ambiguous due to the lack of a simple method for stereochemical assignment. This is an important problem because stereochemistry is a key determinant of biological activity. Here, we report a synthetic DKP library containing all stereoisomers of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro). The library was constructed via a facile microwave-assisted approach. The synthesized library was subjected to spectroscopic characterization using mass spectrometry, NMR, and electronic circular dichroism (ECD). ECD turned out to be a simple yet sensitive method to differentiate all four stereoisomers of each DKP. Thus, our ECD data set can serve as a reference to assign stereochemistry of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) even when available sample is limited. The DKP library is also being examined with biological assays, including biofilm assay, to elucidate stereochemistry-activity relationship.

Valeria Vigo

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