0000000000157199
AUTHOR
Kristina Klinker
showing 13 related works from this author
Combining Orthogonal Reactive Groups in Block Copolymers for Functional Nanoparticle Synthesis in a Single Step.
2017
We report on the synthesis of polysarcosine-block-poly(S-alkylsulfonyl)-l-cysteine block copolymers, which combine three orthogonal addressable groups enabling site-specific conversion of all reactive entities in a single step. The polymers are readily obtained by ring-opening polymerization (ROP) of corresponding α-amino acid N-carboxyanhydrides (NCAs) combining azide and amine chain ends, with a thiol-reactive S-alkylsulfonyl cysteine. Functional group interconversion of chain ends using strain-promoted azide–alkyne cycloaddition (SPAAC) and activated ester chemistry with NHS- and DBCO-containing fluorescent dyes could be readily performed without affecting the cross-linking reaction betw…
Folding induced supramolecular assembly into pH-responsive nanorods with a protein repellent shell
2018
We report the synthesis of ABA' triblock peptide-polysarcosine-peptide conjugates featuring two complementary phenylalanine-histidine pentapeptide strands A/A'. These sequences encode for antiparallel beta-sheet formation into folded conjugates, which promote the self-assembly into polysarcosine-shielded core-shell nanorods. These do not cause aggregation of serum proteins in human blood plasma underlining an enhanced stability.
Polypept(o)ides: Hybrid Systems Based on Polypeptides and Polypeptoids.
2015
Polypept(o)ides combine the multifunctionality and intrinsic stimuli-responsiveness of synthetic polypeptides with the "stealth"-like properties of the polypeptoid polysarcosine (poly(N-methyl glycine)). This class of block copolymers can be synthesized by sequential ring opening polymerization of α-amino acid N-carboxy-anhydrides (NCAs) and correspondingly of the N-substituted glycine N-carboxyanhydride (NNCA). The resulting block copolymers are characterized by Poisson-like molecular weight distributions, full end group integrity, and dispersities below 1.2. While polysarcosine may be able to tackle the currently arising issues regarding the gold standard PEG, including storage diseases i…
Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines
2018
Shielding agents are commonly used to shield polyelectrolyte complexes, e.g. polyplexes, from agglomeration, precipitation in complex media, like blood, and thus enhance their circulation times in vivo. Since up to now primarily poly(ethylene glycol) (PEG) has been investigated to shield non-viral carriers for systemic delivery, we report on the use of polysarcosine (pSar) as a potential alternative for steric stabilization. A redox-sensitive, cationizable lipo-oligomer structure (containing two cholanic acids attached via a bioreducible disulfide linker to an oligoaminoamide backbone in T-shape configuration) was equipped with azide-functionality by solid phase supported synthesis. After m…
Revisiting Secondary Structures in NCA Polymerization: Influences on the Analysis of Protected Polylysines
2014
Two series (degree of polymerization: 20–200) of polylysines with Z and TFA protecting groups were synthesized, and their behavior in a range of analytical methods was investigated. Gel permeation chromatography of the smaller polypeptides reveals a bimodal distribution, which is lost in larger polymers. With the help of GPC, NMR, circular dichroism (CD), and MALDI-TOF, it was demonstrated that the bimodal distribution is not due to terminated chains or other side reactions. Our results indicate that the bimodality is caused by a change in secondary structure of the growing peptide chain that occurs around a degree of polymerization of about 15. This change in secondary structure interferes…
Multidentate Polysarcosine-Based Ligands for Water-Soluble Quantum Dots
2016
We describe the synthesis of heterotelechelic polysarcosine polymers and their use as multidentate ligands in the preparation of stable water-soluble quantum dots (QDs). Orthogonally functionalized polysarcosine with amine and dibenzocyclooctyl (DBCO) end groups is obtained by ring-opening polymerization of N-methylglycine N-carboxyanhydride with DBCO amine as initiator. In a first postpolymerization modification step, the future biological activity of the polymeric ligands is adjusted by modification of the amine terminus. Then, in a second postpolymerization modification step, azide functionalized di- and tridentate anchor compounds are introduced to the DBCO terminus of the polysarcosine…
Sekundärstrukturbildung als Triebkraft für die Selbstorganisation reaktiver Polypept(o)ide: Steuerung von Größe, Form und Funktion kernvernetzter Nan…
2017
Prazise Kontrolle uber Morphologie und Funktion polymerer Nanostrukturen im Rahmen der Selbstorganisation stellt nach wie vor eine Herausforderung im Feld der Material- und biomedizinischen Wissenschaften dar, insbesondere wenn unabhangige Kontrolle uber einzelne Partikeleigenschaften erwunscht ist. Hier wird uber Sekundarstruktur-gesteuerte Selbstorganisation von Nanostrukturen basierend auf amphiphilen Blockcopolypept(o)iden berichtet und eine Strategie zur bio-reversiblen Einstellung der Kernpolaritat und –funktion unabhangig von der Partikelpraparation vorgestellt. Der Peptiden eigene Prozess der Sekundarstrukturbildung erlaubt so die Herstellung spharischer und wurmartiger kernvernetzt…
Exploring new activating groups for reactive cysteine NCAs
2016
Abstract Due to its ability to reversibly crosslink proteins, cysteine has a unique role as an amino acid in nature. For controlled, asymmetric formation of disulfides from two thiols, one thiol needs to be activated. While few activating groups for cysteine have been proposed, they are usually not stable against amines making them unsuitable for solid phase peptide synthesis or amine initiated polymerization of α-amino acid-N-carboxy-anhydrides (NCAs). In this Letter we describe a series of new thiol activated cysteines, as well as their NCAs and explore the link between electron deficiency of the leaving group and control over NCA polymerization.
Evaluating chemical ligation techniques for the synthesis of block copolypeptides, polypeptoids and block copolypept(o)ides: a comparative study
2015
In this work, we describe the synthesis of block copolypeptides, polypeptoids and block copolypept(o)ides by chemical ligation techniques. Polysarcosine (PSar), poly(N-e-trifluoroacetyl-L-lysine) (PLys(TFA)) and poly(γ-benzyl-L-glutamate) (PGlu(OBzl)) homopolymers of different polarities and end group functionalities but with similar average degrees of polymerization (Xn = 50 and 100) could be obtained by ring opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) and postpolymerization modification reactions. In the next step, these polymers were applied to copper(I)-catalyzed azide–alkyne coupling (CuAAC), strain-promoted azide–alkyne coupling (SPAAC) and native chemical l…
Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars
2017
tar-like polymers are one of the smallest systems in the class of core crosslinked polymeric nanoparticles. This article reports on a versatile, straightforward synthesis of three-arm star-like polypept(o)ide (polysarcosine-block-polylysine) polymers, which are designed to be either stable or degradable at elevated levels of glutathione. Polypept(o)ides are a recently introduced class of polymers combining the stealth-like properties of the polypeptoid polysarcosine with the functionality of polypeptides, thus enabling the synthesis of materials completely based on endogenous amino acids. The star-like homo and block copolymers are synthesized by living nucleophilic ring opening polymerizat…
Orthogonally reactive amino acids and end groups in NCA polymerization
2017
Functional amino acids whose reactivity is compatible with the polymerization of α-amino acid-N-carboxyanhydrides (NCAs) have received a lot of attention in recent years. The appeal of these reactive monomers lies in the fact that the resulting polymers can be easily modified in one controlled post-polymerization step, leading to a variety of polypeptidic materials like helical non-natural polycations or glycopeptides. This review highlights recent developments in the field and focuses on the different reactive groups like alkynes, alkenes, azides, chlorides and S-alkylsulfonyls. Furthermore, the modifications after polymerization are discussed, pointing out advantages and challenges. Besid…
Synthesis of Amphiphilic Block Copolypept(o)ides by Bifunctional Initiators: Making PeptoMicelles Redox Sensitive.
2015
In this work, the synthesis of polypeptoid-block-polypeptide copolymers (block copolypept(o)ides) based on bifunctional initiators is described, which introduces a distinct chemical entity at the connection between both blocks. With a view towards redox-sensitive block copolypept(o)ides, a cystamine-based initiator was used to synthesize polysarcosine macroinitiators with degrees of polymerization (Xn) between 100 and 200 displaying monomodal molecular weight distributions and dispersities (Đ) around 1.1 as determined by size exclusion chromatography. Block copolypept(o)ides with a poly(γ-t-butyloxycarbonyl-L-glutamate) (PGlu(O(t) Bu)) block (Xn = 25 or 50) were synthesized by controlled N-…
Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures.
2017
Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple y…