Interfacing native and non-native peptides: using Affimers to recognise α-helix mimicking foldamers

Abstract

Selection methods are used to identify Affimers that recognise α-helix mimicking N-alkylated aromatic oligoamides thus demonstrating foldamer and natural α-amino acid codes are compatible.

Selective Affimers Recognise the BCL‐2 Family Proteins BCL‐xL and MCL‐1 through Noncanonical Structural Motifs**

“…[13][14][15][16] Multiple studies have endeavoured to identify chemotypes which mimic the BH3 domains so as to orthosterically inhibit BCL-2/BH3 PPIs including: constrained peptides, [17][18][19][20][21][22][23] peptidomimetics, [24][25][26][27] small molecules [28][29][30][31] and miniature proteins (identified with assistance from biological selection). [32][33] In this work we have used a previously described Affimer library [34][35][36][37][38][39] to identify ligands for MCL-1, BCL-x L , BCL-2, BAK and BAX and selective inhibitors of MCL-1 and BCL-x L interactions with cognate BH3 partners. Our aim was not only to identify high affinity binders, but also to then screen for subsets that would inhibit PPIs, provide multiple sequences for motif identification, and to use those amenable to structural studies to understand the mode of binding.…”

Selective Affimers Recognize BCL-2 Family Proteins Through Non-Canonical Structural Motifs

“…[13][14][15][16] Multiple studies have endeavoured to identify chemotypes which mimic the BH3 domains so as to orthosterically inhibit BCL-2/BH3 PPIs including: constrained peptides, [17][18][19][20][21][22][23] peptidomimetics, [24][25][26][27] small molecules [28][29][30][31] and miniature proteins (identified with assistance from biological selection). 32,33 We have used a previously described Affimer library [34][35][36][37][38][39] to identify potent ligands for MCL-1, BCL-xL, BCL-2, BAK and BAX and selective inhibitors of MCL-1 and BCL-xL interactions with cognate BH3 partners.…”

Sensitive and selective Affimer-functionalised interdigitated electrode-based capacitive biosensor for Her4 protein tumour biomarker detection

“…Furthermore, Affimers mimic the molecular recognition characteristic of monoclonal antibodies for the detection of biomolecules. Unlike antibodies, Affimers display robust characteristics of low molecular weight, high thermostability, and resistance to extreme pH conditions, ease of site specific functionalization, low production cost with high reproducibly using E. coli recombinant protein expression systems (Arrata et al 2017;Bedford et al 2017;Koutsoumpeli et al 2017;Kyle et al 2015;Raina et al 2015;Rawlings et al 2015;Tiede et al 2014;Vazquez-Lombardi et al 2015;Wang et al 2017b). Of key relevance, there is recent work demonstrating the application of Affimers for biosensing applications (Estrela et al 2010;Ko Ferrigno 2016;Koutsoumpeli et al 2017;Raina et al 2015;Sharma et al 2016;Wang et al 2017b).…”