β-Peptoids: synthesis of a novel dimer having a fully extended conformation

Abstract

Chiral imines 1a,b, already synthesized in our laboratory, were converted in good yield by reduction into the corresponding N-benzyl-γ-lactams 2a,b. Desilylation followed by oxidation of the hydroxymethyl functionality gave the N-benzyl-β-amino acids 5a,b in good yield and high purity. Starting from compound 6a, the corresponding β-peptoid dimer 8 was prepared, together with its derivatives 9 and 10, these latter displaying conformational restriction about the peptide bond, as evidenced by NMR data.

Unveiling the conformational landscape of achiral all-cis tert-butyl β-peptoids

“…S1-S4 † show RMSD and end-toend distances during the simulations. Fluctuation of RMSD is slightly higher for the (+) 8 and (+) 16 structures relative to the alternate (±) 4 and (±) 8 . The end-to-end distance fluctuates between 10-30 Å for octamer and 20-55 Å for 16-mer.…”

“…β-Peptoids are peptidomimetics based on N-alkylated β-amino propionic acid residues. [11][12][13][14][15][16][17] They showed to have remarkable folding propensity, depending on the nature of the side chain, despite the presence of an additional methylene unit. [18][19][20][21][22] The strong ability of the tBu side chain, to lock the cis isomer of the peptoid amide bond, coupled with the larger conformational space generally available in β-peptoids, led us toward the synthesis and extensive conformational analysis of the all-cis tert-butyl β-peptoids, as depicted in Fig.…”

In Vitro ADME Properties of Two Novel Antimicrobial Peptoid-Based Compounds as Potential Agents against Canine Pyoderma

“…Despite this, to date several AMPs are under commercial development [ 25 ]. De novo design of AMPs and peptidomimetics, such as peptoids [ 26 , 27 , 28 , 29 , 30 ], peptide-peptoid hybrids [ 31 , 32 , 33 ] and α-peptide/β-peptoids [ 34 , 35 ] have been successful strategies to increase the in vivo stability. The therapeutic potential of peptoids resides in their biological activity comparable to the parent peptide, and their resistance to proteolytic degradation [ 36 ].…”

Self-Assembled Antimicrobial Nanomaterials

“…AMPs are active selectively at micromolar concentrations and prone to have their chemical synthesis optimized despite their short half-life in vivo and high scaling-up costs of production making difficult the commercial uses [ 25 , 152 ]. De novo design of AMPs following a peptide-mimetic approach [ 153 ] yields peptoids [ 154 , 155 , 156 ], peptide–peptoid hybrids [ 157 ] and α-peptide/β-peptoids [ 158 ] with increased in vivo stability and resistance against proteolytic degradation. Most studies have been performed with short peptoids up to four residues.For example, a recent study described a peptide-peptoid hybrid, B1, and a peptoid, D2, that were highly active against Staphylococcus pseudintermedius (MIC 2–4 µg/mL) and exhibited potential as topical treatment against canine pyoderma [ 152 ].…”