Hydrophobic α,α-Disubstituted Disilylated TESDpg Induces Incipient 3₁₀-Helix in Short Tripeptide Sequence

Abstract

To evaluate the contribution of triethylsilyl α,α-di-n-propylglycine, namely TESDpg, to induce a defined secondary structure, we have prepared model tripeptides in which TESDpg was inserted in three different positions. Studies in solid state and in solution with adapted techniques showed that TESDpg was able to induce a nascent 3 helix in both crystal and solution states.

Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole‐2‐carboxylic acid

“…Particularly promising are silicon-containing amino acids, 4 which may additionally stabilize certain secondary structures. 5 In our opinion, the most interesting case reported to date is the "lipophilic polyproline-II structure" constructed by Martin et al 6 In particular, NMR investigations of an oligomeric sis, prior to the α-helix and much earlier than the hydrophobic motif was recruited by nature. 19 This follows the GC-GCA-GCAU scheme of the genetic code evolution as recently summarized by Hartman and Smith.…”

“…A potential solution to these issues might be offered by the use of strongly lipophilic and bulkier side chains. Particularly promising are silicon‐containing amino acids, which may additionally stabilize certain secondary structures . In our opinion, the most interesting case reported to date is the “lipophilic polyproline‐II structure” constructed by Martin et al In particular, NMR investigations of an oligomeric proline analogue called silaproline (Sip, 1 , Figure ) revealed that the solution structure is dominated by the polyproline‐II (P II ) helix .…”

The Alanine World Model for the Development of the Amino Acid Repertoire in Protein Biosynthesis

“…Another notable class of peptides is peptaibols, the structures with two substitutions at the α-carbon. The simplest structure in this set 2-aminoisobutiric acid, which favors the α-helix, whereas larger substituents can help stabilize other backbone conformations such as 3 10 -helix [45] or fully extended 2.0 5 -helix, an unusual structure not present in natural proteomes [46].…”

Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

“…The insertion of unnatural amino acids (UAAs) in peptides and peptide mimics could add specific features to these molecules, such as proteolytic stability, active functional groups and new reactivity (Clerici et al, 2016; Pellegrino et al, 2016, 2017; Bucci et al, 2017). α,α disubstituted and β- homologs of natural amino acids have been particularly studied during the years for their ability to introduce conformational constrains in peptides and to stabilize specific secondary structures (Bonetti et al, 2015; Pellegrino et al, 2015; Fanelli et al, 2017; Kobayashi et al, 2017). On the other hand, γ UAAs provide a further opportunity to engineer the available backbone through the incorporation of an additional methylene group (Vasudev et al, 2011; Sohora et al, 2018).…”