Nanometer-Sized Amino Acids for the Synthesis of Nanometer-Scale Water-Soluble Molecular Rods of Precise Length

This paper introduces the unnatural amino acid Abc 2K as a nanometer-length building block for the creation of water-soluble molecular rods of exceptional size. Abc 2K is a water-soluble variant of the unnatural amino acid 4‘-amino-[1,1‘-biphenyl]-4-carboxylic acid (Abc) with lysinelike propyloxyammonium side chains at the 2- and 5-positions. The protected building block Fmoc-Abc 2K(Boc) -OH ( 1 ) can be used in standard Fmoc-based solid-phase peptide synthesis to create water-soluble rodlike peptides in nanometer unit lengths up to at least ten nanometers. Oligomers up to and including the decamer were easily prepared on a Rink amide resin. These peptides are easy to purify and characterize by standard reverse-phase HPLC, 1 H NMR, and ESI-MS techniques. The Abc 2K amino acid can be combined with various standard amino acids to provide well behaved hybrid and biologically relevant peptides. Building block 1 is efficiently prepared on a multigram scale from commercially available starting materials by way of the Suzuki cross-coupling reaction. Molecular modeling studies of Abc 2K oligomers show only minor effects from torsional and bending motions and support a model in which the oligomers are relatively straight and rigid. Fluorescence resonance energy transfer (FRET) studies are consistent with a model in which the Abc 2K oligomers behave as rigid rods with a length of 1.0 nm per monomer unit.