The cyclic structure of proline (Pro) confers unique conformational properties on this natural amino acid that influences polypeptide structure and function. Pseudoprolines are a family of Pro isosteres that incorporate a heteroatom, most prominently oxygen or sulfur but also silicon and selenium, to replace the C_β or C_γ carbon atom of the pyrrolidine ring. These readily synthetically accessible structural motifs can facilitate facile molecular editing in a fashion that allows modulation of the amide bond topology of dipeptide elements and influence over ring pucker. While the properties of pseudoprolines have been exploited most prominently in the design of oligopeptide analogues, they have potential application in the design and optimization of small molecules. In this Digest, we summarize the physicochemical properties of pseudoprolines and illustrate their potential in drug discovery by surveying examples of applications in the design of bioactive molecules.

脯氨酸 (Pro) 的环状结构赋予这种影响多肽结构和功能的天然氨基酸独特的构象特性。Pseudoprolines 是 Pro 等排体家族，其中包含一个杂原子，主要是氧或硫，但也包括硅和硒，以取代 C _β或 C _γ吡咯烷环的碳原子。这些易于合成的结构基序可以以一种允许调节二肽元素的酰胺键拓扑结构并影响环褶皱的方式促进简单的分子编辑。虽然假脯氨酸的特性在寡肽类似物的设计中得到了最突出的利用，但它们在小分子的设计和优化中具有潜在的应用。在本文摘中，我们总结了假脯氨酸的物理化学性质，并通过调查生物活性分子设计中的应用实例来说明它们在药物发现中的潜力。