Foldamers in Medicinal Chemistry

Abstract

Bio-inspired synthetic backbones leading to foldamers can provide effective biopolymer mimics with new and improved properties in physiological environment, and in turn could serve as useful tools to study biology and lead to practical appplications in the areas of diagnostics or therapeutics. Remarkable progress has been accomplished over the past 20 years with the discovery of many potent bioactive foldamers originating from diverse backbones and targeting a whole spectrum of bio(macro)molecules such as membranes, protein surfaces & nucleic acids. These current achievements, future opportunities and key challenges that remain will be discussed in this chapter.3 5 Helically folded aliphatic oligomers containing proteinogenic side-chains are classified as biotic helices.

Shaping Macromolecules for Sensing Applications—From Polymer Hydrogels to Foldamers

“…They can be exploited as peptidomimetics [ 43 ], e.g., an additional methylene unit in the β-peptides backbone generates a new stereogenic center and substitution position. This makes them unrecognizable by traditional proteases, which in turn means that they are intrinsically resistant to degradation [ 42 , 163 ]. They can form 8-, 10-, 12-, and 14-helices, depending on the monomer structure guided by the formation of the hydrogen bonds, responsible for structure formation [ 150 , 164 , 165 ].…”

Design of Oligourea-Based Foldamers with Antibacterial and Antifungal Activities

“…To tackle these issues, intense research efforts have been devoted over the last two decades to build synthetic peptidomimetics exhibiting a high propensity to adopt well-defined and predictable folding patterns, referred to as “foldamers” [ 7 ]. This research has produced a variety of artificial backbones decorated with biotic side chains and exhibiting an enhanced stability in biological fluids, thus paving the way to the development of innovative medicines [ 8 , 9 ]. In the field of membrane-active foldamers as antimicrobial agents, noteworthy reports include the work on helically folded peptidomimetic backbones such as helical β-peptides [ 10 ], α,β-peptide hybrids [ 11 ], α-peptoids [ 12 , 13 ], α-peptide/β-peptoid peptidomimetics [ 14 ], γ-peptides [ 15 ], and sulfono-γ-AA peptides [ 16 ].…”

Novel ferrocene imide derivatives: synthesis, conformational analysis and X-ray structure

“…Aromatic foldamers are architectures constructed by linking aromatic monomers with various linkers such as urea [ 1 ], guanidine [ 2 ], or most commonly amide spacers [ 3 , 4 ]. The folding properties of these molecules depend on noncovalent interactions and the conformational properties of the linker, which are determined by steric and electronic factors [ 5 ]. The high stability of the folded structures and the predictability of the folding patterns are remarkable properties of these "abiotic" foldamers [ 6 ].…”