Adamantane‐Terminated Polypeptides: Synthesis by N‐Carboxyanhydride Polymerization and Template‐Based Self‐Assembly of Responsive Nanocontainers via Host–Guest Complexation with β‐Cyclodextrin

Abstract

The synthesis of adamantane‐terminated polypeptides by N‐carboxyanhydride (NCA) polymerization and their use in the template‐based self‐assembly of redox‐responsive nanocontainers is described. Cyclodextrin vesicles (CDV) serve as a supramolecular template to anchor adamantane terminated polypeptides on to the surface of CDV and to form polypeptide shelled vesicles (PPSVss) which are stabilized by crosslinking with cystamin. Polypeptides are characterized by nuclear magnetic resonance, matrix‐assisted laser desorption/ionization (MALDI), and gel permeation chromatography, and nanocontainer formation at each step is confirmed by dynamic light scattering (DLS) and zeta potential measurements. MALDI confirms the presence of the adamantane at the end of the polymers, and isothermal titration calomatry (ITC) of the adamantane‐terminated polypeptides with β‐cyclodextrin proves the capability of adamantane on the polypeptides to form host–guest inclusion complexes even with the longest polypeptides. Encapsulation of a model dye carboxyfluorescein in PPSVss and its redox‐responsive release demonstrates the potential use of this novel type of completely biodegradable and biocompatible nanocontainer for the purpose of intracellullar delivery.

Self‐Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery

“…For the synthesis of Ad terminated polymer, Ad methyl amine (Ad‐NH 2 ) was chosen as the initiator. NCA polymerization of ZLL monomer by this initiator, followed by deprotection of the amines, gave Ad‐PLL as reported in our previous publication [10a] …”

“…This is likely due to the higher molecular weight of Ad‐PLL 52 , which makes the CD cavities inside the NGs inaccessible. In a recent publication, we showed that Ad terminated polypeptides such as Ad‐PLL 52 are able to form host guest complex with β‐CD with a binding affinity, K≈5×10 4 M −1 [10a] . This finding implies that the presence of the polymer on Ad‐PLL 52 does not hinder the host guest interaction of Ad and CD.…”

“…In a recent publication, we showed that Ad terminated polypeptides such as Ad‐PLL 52 are able to form host guest complex with β‐CD with a binding affinity, K≈5×10 4 M −1 . [10a] This finding implies that the presence of the polymer on Ad‐PLL 52 does not hinder the host guest interaction of Ad and CD. The increase in size observed is because of the free CD cavities present on the surface of the NGs, which formed host guest interaction with Ad‐PLL 52 .…”

“…NCA polymerization of ZLL monomer by this initiator, followed by deprotection of the amines, gave Ad‐PLL as reported in our previous publication. [10a] …”

Cyclodextrins as Supramolecular Recognition Systems: Applications in the Fabrication of Electrochemical Sensors

“…Moreover, the CD has a hydrophobic cavity, providing an ideal microenvironment for the enzyme. Among the extensive range of host-guest complexes, the adamantane-β-CD inclusion complex [160] is especially useful in the design of electrochemical-based biosensors [161,162]. The CD adamantane host-guest complex serves to dock the biological recognition element of the sensor, facilitating its recognition of the target analyte.…”