Synthesis of Leishmania mRNA 5′-cap analogs, m 7 Gpppm 2 6 AmpAm (cap-2), and m 7 Gpppm 2 6 AmpAmpCm (cap-3) is reported. Binding affinities of those cap analogs for LeishIF4E proteins were determined using fluorescence spectroscopy. Cap-3 showed similar affinity to LeishIF4Es compared to the mature trypanosomatids cap structure (cap-4).