A catalytic protein–proteomimetic complex: using aromatic oligoamide foldamers as activators of RNase S

Abstract

An aromatic oligoamide foldamer acts as an α-helix mimetic and binds to the RNase S-protein resulting in restoration of its catalytic function.

Natural and Synthetic Oligoarylamides: Privileged Structures for Medical Applications

“…In addition, it was found that hybrid architectures closely related to 42 – 44 replace a segment of the protein structure (the S‐peptide from RNase S) with a foldamer that itself mimics this α‐helix. Interestingly, such a non‐covalent complex with the S protein led to the restoration of catalytic function, thus showing that the foldamers can act as a component of a functional quaternary structure that performs RNA hydrolysis [83] …”

“…Interestingly, such an on-covalentc omplex with the Sp rotein led to the restoration of catalytic function, thus showing that the foldamers can act as acomponent of afunctional quaternary structure that performs RNA hydrolysis. [83] In addition to the O-alkylated foldamersd iscussed in detail here,t here is one work on corresponding trimeric N-alkylated oligoamidest hat effectively bind hDM2 by mimicking key residues of p53. In addition, these proteomimetics have also been shownt ob ind Mcl-1/NOXA-B in both biophysical assays and in ac ellular context.…”

Influence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamides

“…Whilst there is a diverse array of anticancer agents currently used in the clinic, small organic molecules, for example, lenalidoamide and flutamide, represent an important group of chemotherapeutic agents. Aromatic oligoamides ( Hamuro et al, 1994 ; Hamuro et al, 1996 ; Yuan et al, 2004 ; Yuan et al, 2005 ; Kortelainen et al, 2015 ) are a class of small organic compounds that have been shown to possess potential anticancer activity ( Tew et al, 2002 ; Ernst et al, 2003 ; Yin and Hamilton, 2005 ; Davis et al, 2007 ; Plante et al, 2009 ; Azzarito et al, 2012 ; Burslem et al, 2014 ; Jayatunga et al, 2014 ; Burslem et al, 2016 ) and have also been employed in a wide range of applications including catalysis, ( Hegedus et al, 2019 ), sensing, ( Yi et al, 2005 ; Bao et al, 2008 ; Yamato et al, 2009 ), materials chemistry ( König et al, 2000 ; Garía et al, 2010 ) and crystal engineering. ( Suhonen et al, 2016 ; Annala et al, 2017 ).…”

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.…”