Cysteine‐Containing Polyisocyanides as Versatile Nanoplatforms for Chromophoric and Bioscaffolding

Abstract

The straightforward syntheses of polyisocyanides containing the alanine-cysteine motif in their side chains have been achieved. Detailed characterization of the polymers revealed a well-defined and highly stable helical conformation of the polyimine backbone responsible for the formation of rodlike structures of over one hundred nanometers. The 4(1) helix is further stabilized by beta-sheet-like interactions between the peptide arms. As a result, the cysteine sulfur atoms are regularly aligned along the polymer axis, which provides a unique platform for the scaffolding of various entities by using versatile click-chemistry postmodification approaches. For instance, pyrene derivatives were introduced through thio-specific reactions involving either maleimide, iodoacetamide, or thioester groups, leading to arrays of stacked chromophores with excimer-like emission. A water-soluble cysteine-rich polyisocyanide was successfully biotinylated and coupled to streptavidin.

Solid-state NMR characterization of tri-ethyleneglycol grafted polyisocyanopeptides

“…Circular dichroism (CD) is sensitive to the helical backbone conformation, and the CD spectra on the polymers deny a 1 : 1 distribution of two different helices, while on the other, the doubled resonances are close to a 1 : 1 ratio. Literature data also report on a preferred type of PICs' helix depending on the pendant groups …”

“…Since then, a great variety of helical macromolecules was published . A well‐known class of synthetic helical polymers is based on polyisocyanides (PICs) . Upon the polymerization of the isocyanide monomers, a twisted structure is formed as a result of the merry‐go‐round mechanism at the nickel catalyst center .…”

“…To optimize performance and adjust hydrogel properties, however, it is essential to understand the molecular mechanisms of gel formation. So far, oligo(ethylene glycol)‐substituted PICs hydrogels have mainly been studied macroscopically, and although the macroscopic mechanical properties are well explained using mechanical models, the molecular origin of the bundling and gel formation is still poorly understood. NMR is a method that provides structural and dynamic information with a chemical group specific resolution, is sensitive, and additionally, does not require specific sample preparation procedures.…”

Multivalent Protein Assembly Using Monovalent Self-Assembling Building Blocks

“…The occurrence of up to seven discrete protein bands indicates as well the assembly of multiple discotics into longer stacks, which enable the binding of at least seven monovalent streptavidins. The formation of discrete protein bands is in contrast to biotinylated polymers [40], which when bound to labeled streptavidin result in a smear on the gel. This indicated that the formed supramolecular polymers are much smaller than the size of streptavidin, which through their larger size are the main size determining factor.…”

Cysteine Isocyanide in Multicomponent Reaction: Synthesis of Peptido-Mimetic 1,3-Azoles

“…Moreover, dipeptide isocyanide bearing cysteine derivatives with an S -ethyl carbamate protecting group have been recently described for the synthesis of polyisocyanides. 19 In another report, ( R )-methyl 3-(benzythio)-2-isocyanopropanoate was described for the synthesis of corresponding isoselenocyanate. 20 However, benzyl protection for thiol is not promising for many postmodifications on sulfur.…”