Transforming Thymidine into a Magnetic Resonance Imaging Probe for Monitoring Gene Expression

摘要: Synthetic chemistry has revolutionized the understanding of many biological systems. Small compounds that act as agonists and antagonists proteins, occasionally imaging probes, have contributed tremendously to elucidation pathways. Nevertheless, function thousands proteins is still elusive, designing new probes remains a challenge. Through screening characterization, we identified thymidine analogue probe for expression herpes simplex virus type-1 kinase (HSV1-TK). To detect probe, used chemical exchange saturation transfer magnetic resonance (CEST-MRI), in which dynamic process between an exchangeable proton surrounding water protons amplify desired contrast. Initially, five pyrimidine-based molecules were recognized putative agents, since their imino resonate at 5-6 ppm from frequency detection therefore less affected by endogenous CEST contrast or confounded direct saturation. Increasing pK(a) value reduction its 5,6-double bond results significant rate (k(ex)) this protons. This reduced k(ex) dihydropyrimidine nucleosides fulfills "slow intermediate regime" condition generating high CEST-MRI Consequently, 5-methyl-5,6-dihydrothymidine optimal demonstrated feasibility vivo HSV1-TK. In light these findings, approach can be generalized specific variety enzymes.