Ngambenjawong Chayanon, Gustafson Heather H, Sylvestre Meilyn, Pun Suzie H
Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Ave NE, Foege, Seattle, WA, 98195, USA.
Chembiochem. 2017 Dec 14;18(24):2395-2398. doi: 10.1002/cbic.201700446. Epub 2017 Nov 7.
Peptides are a growing class of macromolecules used in pharmaceutics. The path toward the clinical use of candidate peptides involves sequence optimization and cyclization for stability and affinity. For internalized peptides, tagging is also often required for intracellular trafficking studies, although fluorophore conjugation has an impact on peptide binding, permeability, and localization. Herein, a strategy based on cysteine arylation with tetrafluoroterephthalonitrile (4F-2CN), which simultaneously cyclizes peptides and imparts fluorescence, is reported. The 4F-2CN cyclization of an M2 macrophage-targeting peptide yields, in a single step, a peptide with improved serum stability, intrinsic fluorescence, and increased binding affinity. In a murine breast cancer model, it is demonstrated that the intrinsic fluorescence from the cyclized peptide is sufficient for monitoring biodistribution by whole-organ fluorescence imaging and cell internalization by flow cytometry.
肽是制药领域中一类不断发展的大分子。候选肽临床应用的途径包括进行序列优化和环化以提高稳定性和亲和力。对于内化肽，尽管荧光团偶联会影响肽的结合、通透性和定位，但在细胞内运输研究中通常也需要进行标记。在此，报道了一种基于用四氟对苯二甲腈（4F-2CN）进行半胱氨酸芳基化的策略，该策略可同时使肽环化并赋予其荧光。一种靶向M2巨噬细胞的肽经4F-2CN环化，一步即可得到一种具有更高血清稳定性、固有荧光和增加结合亲和力的肽。在小鼠乳腺癌模型中，证明了环化肽的固有荧光足以通过全器官荧光成像监测生物分布，并通过流式细胞术监测细胞内化情况。
