Martin Hannah S, Podolsky Kira A, Devaraj Neal K
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
Chembiochem. 2021 Nov 16;22(22):3148-3157. doi: 10.1002/cbic.202100232. Epub 2021 Aug 6.
Nucleotides, amino acids, sugars, and lipids are almost ubiquitously homochiral within individual cells on Earth. While oligonucleotides and proteins exist as one natural chirality throughout the tree of life, two stereoisomers of phospholipids have separately emerged in archaea and bacteria, an evolutionary divergence known as "the lipid divide". Within this review, we focus on the emergence of phospholipid homochirality and compare the stability of synthetic homochiral and heterochiral membranes in vitro. We discuss chemical probes designed to study the stereospecific interactions of lipid membranes in vitro. Overall, we aim to highlight studies that help elucidate the determinants of stereospecific interactions between lipids, peptides, and small molecule ligands. Continued work in understanding the drivers of favorable interactions between chiral molecules and biological membranes will lead to the design of increasingly selective chemical tools for bioorthogonal labeling of lipid membranes and safer membrane-associating pharmaceuticals.
在地球上，核苷酸、氨基酸、糖类和脂质在单个细胞内几乎普遍呈同手性。虽然寡核苷酸和蛋白质在整个生命之树中以一种天然手性存在，但磷脂的两种立体异构体分别在古细菌和细菌中出现，这种进化上的差异被称为“脂质分歧”。在这篇综述中，我们聚焦于磷脂同手性的出现，并比较合成的同手性和异手性膜在体外的稳定性。我们讨论了旨在研究脂质膜体外立体特异性相互作用的化学探针。总体而言，我们旨在突出有助于阐明脂质、肽和小分子配体之间立体特异性相互作用决定因素的研究。在理解手性分子与生物膜之间有利相互作用的驱动因素方面持续开展的工作，将导致设计出越来越具选择性用于脂质膜生物正交标记的化学工具以及更安全的膜结合药物。
