Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 10;22(5):2171-2180.
doi: 10.1021/acs.biomac.1c00253. Epub 2021 Apr 8.

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

Tobias A Bauer  1   2 , Jan Imschweiler  2 , Christian Muhl  1   2 , Benjamin Weber  2 , Matthias Barz  1   2
Affiliations

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

Tobias A Bauer et al. Biomacromolecules. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following competing financial interest(s): Matthias Barz holds the patent Thiol-protected amino acid derivatives and uses thereof WO2015169908A1.

Figures

Scheme 1
Scheme 1. Synthesis of Block Copolypept(o)ides with Varying Secondary Structures
Figure 1
Figure 1
Analytical gel permeation chromatography in HFIP. (A) pSar-b-p(dl)Cys (P3–P6), (B) pSar-b-p(l)Cys (P7–P10), and (C) pSar-b-p(l)Hcy (P11–P14), with the respective pSar macroinitiators (P1 and P2).
Figure 2
Figure 2
Secondary structure analysis of pSar-b-p(dl)Cys, pSar-b-p(l)Cys, and pSar-b-p(l)Hcy. (A) FT-IR spectroscopy and (B) 1H NMR spectroscopy.
Figure 3
Figure 3
Influence of the secondary structure on the aggregation behavior. (A) Schematic illustration of the dynamic range. (B) Aggregation curve of polypept(o)ides (P3, P7, and P11) with sigmoidal fit.
Figure 4
Figure 4
Aggregation curves for copolymers P3–P14. (A) pSar-b-p(dl)Cys, (B) pSar-b-p(l)Cys, and (C) pSar-b-p(l)Hcy.
Figure 5
Figure 5
Self-assembly and core cross-linking. (A) Schematic illustration of secondary structure-driven self-assembly. (B) Single-angle DLS analysis of polymeric micelles (left: pSar-b-p(dl)Cys and pSar-b-p(l)Cys, right: pSar-b-p(l)Hcy). Morphological analysis of core cross-linked polymeric micelles by AFM and cryoTEM: (C) pSar-b-p(dl)Cys, (D) pSar-b-p(l)Cys, and (E) pSar-b-p(l)Hcy.
See this image and copyright information in PMC

References

    1. Bonduelle C. Secondary Structures of Synthetic Polypeptide Polymers. Polym. Chem. 2018, 9, 1517–1529. 10.1039/C7PY01725A. - DOI
    1. Kricheldorf H. R.; Müller D. Secondary Structure of Peptides. Polym. Bull. 1983, 10, 513–520. 10.1007/BF00285369. - DOI
    1. Deng C.; Wu J.; Cheng R.; Meng F.; Klok H. A.; Zhong Z. Functional Polypeptide and Hybrid Materials: Precision Synthesis via α-Amino Acid N-Carboxyanhydride Polymerization and Emerging Biomedical Applications. Prog. Polym. Sci. 2014, 39, 330–364. 10.1016/j.progpolymsci.2013.10.008. - DOI
    1. Van Beek J. D.; Beaulieu L.; Schäfer H.; Demura M.; Asakura T.; Meier B. H. Solid-State NMR Determination of the Secondary Structure of Samia Cynthia Ricini Silk. Nature 2000, 405, 1077–1079. 10.1038/35016625. - DOI - PubMed
    1. Vollrath F.; Knight D. P. Liquid Crystalline Spinning of Spider Silk. Nature 2001, 410, 541–548. 10.1038/35069000. - DOI - PubMed

Publication types

LinkOut - more resources