Secondary Structure-Driven Self-Assembly of Thiol-Reactive Polypept(o)ides

Biomacromolecules, vol. 22, pp. 2171–2180

Abstract

High Resolution Image Download MS PowerPoint Slide Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or β-sheets represent an additional parameter to direct self-assembly and the morphology of nanostructures. We investigated the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypept(o)ides. The individual morphologies can be preserved by core cross-linking via chemoselective disulfide bond formation. A series of thiol-responsive copolymers of racemic polysarcosine- block -poly( S -ethylsulfonyl- dl -cysteine) (pSar- b -p( dl )Cys), enantiopure polysarcosine- block -poly( S -ethylsulfonyl- l -cysteine) (pSar- b -p( l )Cys), and polysarcosine- block -poly( S -ethylsulfonyl- l -homocysteine) (pSar- b -p( l )Hcy) was prepared by N -carboxyanhydride polymerization. The secondary structure of the peptide segment varies from α-helices (pSar- b -p( l )Hcy) to antiparallel β-sheets (pSar- b -p( l )Cys) and disrupted β-sheets (pSar- b -p( dl )Cys). When subjected to nanoprecipitation, copolymers with antiparallel β-sheets display the strongest tendency to self-assemble, whereas disrupted β-sheets hardly induce aggregation. This translates to worm-like micelles, solely spherical micelles, or ellipsoidal structures, as analyzed by atomic force microscopy and cryogenic transmission electron microscopy, which underlines the potential of secondary structure-driven self-assembly of synthetic polypeptides.

Authors 4

1. Tobias Alexander Bauer Aachen Leiden Academic Centre for Drug Research

   Leiden University · Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany

   Leiden Academic Centre for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

2. Jan Imschweiler

   Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany

3. Benjamin Weber

   Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany

4. Matthias Barz corresponding Aachen Leiden Academic Centre for Drug Research

   Leiden University · Johannes Gutenberg University Mainz

   Affiliation as printed

   Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany

   Leiden Academic Centre for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands