Chemistry, Virginia Commonwealth University, 1001 W Main St, Richmond, VA-23284, USA.
Massey Cancer Center, Virginia Commonwealth University, 1001 W Main St, Richmond, VA-23284, USA.
Chembiochem. 2023 Jun 1;24(11):e202300020. doi: 10.1002/cbic.202300020. Epub 2023 May 8.
Macrocyclization has proven to be a beneficial strategy to improve upon some of the disadvantages of peptides as therapeutics. Nevertheless, many peptide cyclization strategies are not compatible with in vitro display technologies like mRNA display. Here we describe the novel amino acid p-chloropropynyl phenylalanine (pCPF). pCPF is a substrate for a mutant phenylalanyl-tRNA synthetase and its introduction into peptides via in vitro translation leads to spontaneous peptide macrocyclization in the presence of peptides containing cysteine. Macrocyclization occurs efficiently with a wide variety of ring sizes. Moreover, pCPF can be reacted with thiols after charging onto tRNA, enabling the testing of diverse ncAAs in translation. The versatility of pCPF should facilitate downstream studies of translation and enable the creation of novel macrocyclic peptide libraries.
环化已被证明是一种有益的策略，可以改善肽作为治疗剂的一些缺点。然而，许多肽环化策略与体外展示技术如 mRNA 展示不兼容。在这里，我们描述了一种新型氨基酸 p-氯丙炔基苯丙氨酸 (pCPF)。pCPF 是一种突变苯丙氨酸 tRNA 合成酶的底物，其通过体外翻译引入到肽中，在含有半胱氨酸的肽存在下导致肽的自发环化。环化反应可以高效进行，并且具有多种环大小。此外，pCPF 可以在与 tRNA 结合后与硫醇反应，从而可以在翻译中测试各种 ncAA。pCPF 的多功能性应该有助于下游翻译研究，并能够创建新型的大环肽文库。
