Chemistry and supramolecular chemistry of the iota-amino acid aminodiphenylmethanecarboxylic acid (Adc) and its derivatives

Chemists have endeavored to design and synthesize alternative biopolymers that mimic biological functions. Notable biopolymers include proteins, nucleic acids and polysaccharides, which consist of simple monomers, such as alpha-amino acids, nucleotides, and sugar units, respectively. These biopolymers use non-covalent interactions among the non-adjacent monomers to bring molecules together into compact, well-defined structures to achieve specific functions. The details of how biological systems achieve their task in response to the environment have inspired many chemists to develop new molecular systems through rational design.; We envision new synthetic systems, which comprise unnatural building blocks. To construct the synthetic systems that mimic the biopolymers, I used a class of unnatural building block, called aminodiphenylmethanecarboxylic acid (Adc). The Adc building block can be thought of as an analogue of the alpha-amino acid glycine that has been enlarged fourfold by insertion of two benzene rings into the main-chain bonds. The large size of Adc monomer permits rapid synthesis of large synthetic macromolecules compatible in size to the biopolymers. The structural rigidity and fixed geometry of the Adc building block should potentially facilitate the formation of macrocyclic peptides or helical linear peptides.; An aminopropoxy side chain (-OCH2CH2CH 2NH2) at the beta-carbon of the Adc makes a hydrogen bond to the adjacent amide NH group to prevent possible intermolecular hydrogen bonding and increases water-solubility. The side chain resembles that of lysine amino acid, and we refer this derivative as "AdcK". Chapter I discusses the synthesis, structural studies, and binding properties of water-soluble macrocyclic peptides based on AdcK building blocks. Chapter II discusses the synthesis of sequence-specific macrocyclic peptides, displaying four different substituents at the periphery by solid-phase peptide synthesis. Lastly, in Chapter III, studies of linear peptides explore the effect of non-covalent interactions towards the formation of solution structures, particularly in aqueous solution. As an ongoing effort, I will also discuss structural adaptations and refinements of the Adc building blocks based on the structural studies of the linear iota-peptides.