Design and automated generation of artificial estrogen receptor as potential endocrine disruptor chemical binders

Shortcut Access to Peptidosteroid Conjugates: Building Blocks for Solid-Phase Bile Acid Scaffold Decoration by Convergent Ligation

“…Further attracted by the popularity of the contemporary Huisgen click and Staudinger ligation chemistries, more interesting opportunities in that direction were found during synthesis of the aforementioned EDC sensor conjugates 7 , more specifically through one of the intermediates featuring an azide functionality as orthogonal protection for the corresponding amine and an alkyne moiety for later screening purposes [ 36 ]. An example of such efforts towards template-assembled multivalent triazole conjugates by decorating a cyclic decameric peptide scaffold has been recently contributed by Avrutina et al .…”

“…Upon Alloc deprotection, azidoacetic acid was smoothly coupled to provide the azide functionality and complete the synthesis of our second ligation template 15 . Optimized earlier [ 36 ], Alloc deprotection was achieved using phenyl silane (PhSiH 3 , 25 eq.) as allyl group scavenger, combined with Pd(0) tetrakistriphenylphosphine [Pd(PPh 3 ) 4 , 0.1 eq.]…”

“…This allowed for further generation of loop structures 6 (incorporating longer peptide sequences) as synthetic vaccines against the measles virus [ 30 , 31 ], complementing the few successful attempts towards preparation of both cyclic [ 15 , 20 ] and cyclodimeric peptidosteroid macrocycles [ 32 , 33 , 34 , 35 ] in literature. Most recently, the established methodologies allowed for the parallel solid-phase synthesis of a first generation of receptors 7 for endocrine disruptor chemicals (EDCs) [ 36 ], while the architectural features of the bile acid framework were further exploited in the development of zipper-type transcription factor miniatures by heterodimeric tweezer models 8 , based on building block 4 [ 37 ]. Whereas all constructs depicted in Figure 2 were synthesized by consecutive chain elongation through stepwise linear SPPS procedures, our current interest has shifted towards the possibilities of contemporary ligation schemes for the convergent assembly of our peptidosteroid targets on solid-phase.…”

Untapped Opportunities of Resin‐to‐Resin Transfer Reactions (RRTR) for the Convergent Assembly of Multivalent Peptide Conjugates

“…Selective Alloc deprotection of the next amine group, located at the C3‐position of intermediate conjugate 3 , was carried out with previously optimized conditions . In the context of our research on artificial receptor and minimized protein models, the RRTR methodology seemed attractive towards a faster (library) optimization of such designs . Therefore, we decided to use donor resin 1 for a second time, to assemble a truncated test model derived from the homodimeric GCN4 leucine zipper .…”

“…[63,64] In the context of our research on artificial receptor and minimized protein models, the RRTR methodology seemed attractive towards a faster (library) optimization of such designs. [65][66][67] Therefore, we decidedt ou se donor resin 1 forasecond time, to assemble a truncated test model derived from the homodimeric GCN4 leucine zipper. [68] Ag amma-aminobutyric acid (GABA) spacerw as installed prior to the RRTR step, to alleviates teric constraints typical for our steroid-baseda rchitecture.…”