Synthesis and properties of the anticodon stem-loop of human mitochondrial tRNAMet containing the disease-related G or m1G nucleosides at position 37

A single point mutation (A4435G) in the human mitochondrial tRNAMet (hmt-tRNAMet) gene causes severe mitochondrial disorders associated with hypertension, type 2 diabetes and LHON. This mutation leads to the exchange of A37 in the anticodon loop of hmt-tRNAMet for G37 and 1-methylguanosine (m1G37). Here we present the first synthesis and structural/biophysical studies of the anticodon stem and loop of pathogenic hmt-tRNAsMet.