Transition of Conformation and Solubility in β-Sheet-Structured Poly(l-cysteine)s with Methylthio or Sulfonium Pendants

Abstract

Poly(L-cysteine)s with methylthio pendants (PMTLCs) were synthesized by ring-opening polymerization of a new L-cysteine-based Ncarboxyanhydride. The thioether bonds of PMTLC can be readily oxidized by H 2 O 2 yielding water-soluble PMTLC OX . The methylthio groups can undergo an alkylation reaction using methyl iodide and a subsequent ion-exchange reaction yielding sulfonium-based polypeptides (PPLC-DMS-X, where X = I, BF 4 ). PPLC-DMS-X showed upper critical solution temperature-type thermo-and oxidationresponsive properties in aqueous solutions. Both PMTLC and PPLC-DMS-X showed oxidation-induced β-sheet to α-helix transitions. The absorbance of PPLC-DMS-I and methyl orange aqueous solution displayed a significant linear correlation with temperature, which makes the sulfonium-based polypeptides good candidates in the field of temperature sensors.

Poly(l-cysteine) Peptide Amphiphile Derivatives Containing Disulfide Bonds: Synthesis, Self-Assembly-Induced β-Sheet Nanostructures, pH/Reduction Dual Response, and Drug Release

“…As shown in Figure b, it is clearly observed that the samples exhibit strong amide I and II bands at 1635 and 1525 cm –1 , respectively, indicating that the β-sheet is a predominant conformation of alkyl-P­(Cys-SS-CH 2 CH 2 COOH). This result is consistent with the fact that poly­( l -cysteine) exclusively forms a β-sheet structure. ,, It should be noted that the secondary structure of the PAs varied depending on the state of the PAs.…”

“…This result is consistent with the fact that poly(L-cysteine) exclusively forms a β-sheet structure. 22,23,39 It should be noted that the secondary structure of the PAs varied depending on the state of the PAs.…”

“…20 L-cysteine is a natural amino acid, and its homopolymer [i.e., poly(L-cysteine)] exclusively forms β-sheet structures. 22,23 The chemically reactive thiol group of L-cysteine can be readily modified to form thioether (−S−), 24−27 thiocarbonate [−S− C(O)−O−], 28 or disulfide (−SS−) bonds, 29−31 which have been employed to construct side-chain-modified peptides with various functions. In contrast to thioether and thiocarbonate, disulfide shows a significant superiority for drug delivery because of its ability to undergo a thiol−disulfide exchange in intracellular reductive environments.…”

“…l -cysteine is a natural amino acid, and its homopolymer [i.e., poly­( l -cysteine)] exclusively forms β-sheet structures. , The chemically reactive thiol group of l -cysteine can be readily modified to form thioether (−S−), − thiocarbonate [−S–C­(O)–O−], or disulfide (−SS−) bonds, − which have been employed to construct side-chain-modified peptides with various functions. In contrast to thioether and thiocarbonate, disulfide shows a significant superiority for drug delivery because of its ability to undergo a thiol–disulfide exchange in intracellular reductive environments. , In this work, we report a class of disulfide bond-containing PAs (PA1–PA3, Figure a) with different lengths of alkyl tails prepared by ROP of α-amino acid NCA and the PPM route, namely, alkyl-poly­( S -(((2-carboxyethyl)­thio)- l -cysteine) (alkyl-P­(Cys-SS-CH 2 CH 2 COOH)).…”

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

“…On the other hand, polymerizations of 𝛼-amino acid NTAs in amide polar solvents are still regarded difficult as the bimolecular termination is inevitable, whereas polar solvents such as DMF are common for NCA polymerizations. [109][110][111] Due to limited initiators and slow polymerization rates, designs of efficient catalysts and initiators for controlled polymerizations of NTAs are an intriguing topic. Moreover, the polymerizations of NTA and NNTA monomers with unprotected functional groups, especially thiol and hydroxyl groups, are rarely reported.…”