Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers

Abstract

Mimicking the molecular recognition functionality of antibodies is a great challenge. Foldamers are attractive candidates because of their relatively small size and designable interaction surface. This paper describes a sandwich type enzyme-linked immunoassay with a tetravalent β-peptide foldamer helix array as capture element and enzyme labeled tracer antibodies. The assay was found to be selective to β-amyloid oligomeric species with surface features transiently present in ongoing aggregation. In optimized conditions, with special emphasis on the foldamer immobilization, a detection limit of 5 pM was achieved with a linear range of 10 -500 pM. These results suggest that protein mimetic foldamers can be useful tools in biosensors and affinity assays.

Structural Optimization of Foldamer-Dendrimer Conjugates as Multivalent Agents against the Toxic Effects of Amyloid Beta Oligomers

“…To study the role of certain structure elements in the binding affinity, a set of new foldamer sequences were designed ( Figure 2 ) and ligated to lysine-dendron scaffolds having a focal symmetry. This template with biotin affinity tag can be easily synthesized by solid phase peptide synthesis and immobilized on a streptavidin coated support such as the surface of the ELISA plate [ 36 ]. Structural changes included fine-tuning the side-chain properties ( 2b – 2d ), changing the position of ionic residues ( 2e ) and introducing bulky bicyclic side-chains ( 2f – 2i ).…”

Shaping Macromolecules for Sensing Applications—From Polymer Hydrogels to Foldamers

“…Thanks to the structural control of foldamers, they can be designed to bind complementary guests [ 178 ], e.g., cations [ 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ], anions [ 186 , 187 , 188 , 189 , 190 , 191 , 192 ], or non-charged molecules [ 164 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 ]. They have been applied in the detection of metal ions [ 210 , 211 , 212 , 213 ], explosives [ 214 ], biomarkers [ 215 ], pH [ 216 , 217 ], membrane curvature [ 218 ], and fructose [ 198 ] ( Table 3 ).…”

“…Martinek et al designed an ELISA-foldamer test for sensing Aβ-oligomers which plays a key role in the pathogenesis of Alzheimer’s disease [ 215 ]. The scientists have created a sandwich test consisting of a biotin-labeled foldamer immobilized on streptavidin-coated plates.…”

“…Studies have confirmed its selectivity for Aβ surface patterns transiently present during the ongoing aggregation process. These results imply that protein mimicking foldamers could be useful agents in biosensors and affinity assays [ 215 ].…”

Proteomimetic surface fragments distinguish targets by function

“…[1][2][3] Although pioneering studies demonstrated the possibility of ribosome-assisted coupling of amino acids with non-natural backbones, [4][5][6][7] in vitro directed evolutionary approaches 8 are not routinely available for searching and optimization of fundamentally xenobiotic surface mimetic structures. [9][10][11] Four major experimental chemical approaches and their combinations have been applied to address this problem: (i) screening of large surface mimetic libraries, 10,12,13 (ii) topdown mutational design based on known ligands, [14][15][16][17][18][19][20][21] (iii) bottom-up design and assembly starting from structural hypotheses, 3,[22][23][24][25][26][27][28][29][30][31] and (iv) the fragment-centric system chemistry approach leading to self-assembling ligands. 32 Recent theoretical and experimental results strongly support that fragment-centric design built on recognition elements of reduced structural complexity is highly promising for the construction of surface mimetic ligands.…”