FIGURE 1.

A, synthesis of [Bmt¹]- and [Sar³]-substituted analogues by olefin cross-metathesis and alkylation. Reagents were DCM, Hoveyda-Grubbs catalyst, second generation, reflux, 30 h (i) and ethyl acetate reflux (ii). B, structure of SmBzCsA. C, the crystal structure of SmBzCsA (Protein Data Bank code 4IPZ) is shown bound to CypA (solid magenta surface). The aligned structure of CypD (Protein Data Bank code 5A0E) is shown as a wire mesh. Amino acids 9 to 2 are involved in cyclophilin binding. The [Bmt¹] residue (pink) side chain and the [Sar³] substituent do not affect cyclophilin binding.