A Unique and Stable Polyproline I Helix Sorted out from Conformational Equilibrium by Solvent Polarity

Abstract

Polyproline I helical structures are often considered as the hidden face of their most famous geminal sibling, Polyproline II, as PPI is generally spotted only within a conformational equilibrium. We designed and synthesized a stable Polyproline I structure exploiting the striking tendency of (S)-indoline-2-carboxylic acid to drive the peptide bond conformation toward the cis amide isomer, when dissolved in polar solvents. The cooperative effect of only four amino acidic units is sufficient to form a preferential structure in solution. We shed light on this rare secondary structure with a thorough analysis of the spectroscopic and chiroptical properties of the tetramer, supported by X-ray crystallography and computational studies.

Ultrasensitive Solvatochirochromism of Single Benzene Chromophores

“…Upon structural optimization and calculation, the ECD intensity of the two conformers displayed slight differences (Figure S17). From the NMR data, there are no clearly distinguishable groups of peaks to identify cis‐ or trans‐ like conformers compared to previous works [65,66] . Instead, only peak shifts were observed as the solvent changes.…”

“…From the NMR data, there are no clearly distinguishable groups of peaks to identify cis-or translike conformers compared to previous works. [65,66] Instead, only peak shifts were observed as the solvent changes. Therefore, the conformational changes should not be neglected, but the solute-solvent interactions play a major role in the chiroptical responses.…”

Influence of heterochirality on the structure, dynamics, biological properties of cyclic(PFPF) tetrapeptides obtained by solvent-free ball mill mechanosynthesis

“…47 Its particular sensitivity is seen in study of biomolecules, including, in particular, peptides. [48][49][50][51][52] As can be seen in Figure 8a-b, the ECD/UV spectra of samples A and B recorded in the mixture of CH 3 CN/H 2 O (1:1) are similar in the whole spectral range. The only notable difference between ECD spectra lies in the intensity of the negative band(s) centred at ~198 nm; ECD spectrum of A is ~1.7 times more intense.…”

Design of Triazolium-Grafted Peptidomimetic Macrocycles with Facial Amphipathicity to Target Pathogenic Bacteria

“…Two tetramers ( 1 – 2 ), two hexamers ( 3 – 4 ), and an octamer ( 5 ) were obtained in yields ranging from 45% to 62% (Scheme , Supporting Information (SI)). Head-to-tail cyclization efficiency was evaluated using a panel of coupling reagents: the carbodiimide EDCI in the presence of HOBt, the phosphonium PyBOP, , the uronium agents HATU and COMU, and the Mukaiyama reagent . This preliminary study quickly went in favor of HATU since other coupling reagents led to macrocycles with yields not exceeding 10%.…”

“…Head-to-tail cyclization efficiency was evaluated using a panel of coupling reagents: the carbodiimide EDCI in the presence of HOBt, 15 the phosphonium PyBOP, 8b,16 the uronium agents HATU 16 and COMU, 17 and the Mukaiyama reagent. 18 This preliminary study quickly went in favor of HATU since other coupling reagents led to macrocycles with yields not exceeding 10%. An additional level of optimization was carried out with HATU/ DIPEA, varying the number of equivalents, solvent (DCM or DMF), and concentration (Scheme 1).…”