Helical Nonfouling Polypeptides for Biomedical Applications

Zhang, Chong; Lu, Hua

doi:10.1007/s10118-022-2688-2

Cited by 8 publications

(7 citation statements)

References 182 publications

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“…More importantly, unlike other stimuli-responsive polymers, the peptide segments fold back into α-helix in a highly precise way. In such a structure, the amino acid residues are arranged so that intramolecular hydrogen bonds could form between the oxygen of the CO of amino acid residue i and the hydrogen of the N–H group of the bond four amino acid residues below it in the helix ( i + 4). − For this reason, the newly formed helical structure is almost identical to the original one. Therefore, the shape of the imprint cavities could be largely restored.…”

Section: Results and Discussionmentioning

confidence: 99%

Molecularly Imprinted Polymers with Shape-Memorable Imprint Cavities for Efficient Separation of Hemoglobin from Blood

Dong

Guan

et al. 2023

Biomacromolecules

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Efficient separation and purification of hemoglobin from blood and other complicated biological fluids still remains a big challenge. Molecularly imprinted polymers (MIPs) of hemoglobin are potential choices; however, they suffer from severe problems including difficult template removal and low imprinting efficiency like other protein-imprinted polymers. Herein, a novel MIP of bovine hemoglobin (BHb) was designed in which a peptide crosslinker (PC), instead of the commonly used crosslinkers, was used. The PC, a random copolymer of lysine and alanine, adopts an α-helical conformation at pH 10 but transits to a random coil conformation at pH 5. The introduction of alanine residues lowers the pH range at which the PC undergoes helix-coil transition. The imprint cavities in the polymers are shape-memorable due to the reversible and precise helix-coil transition of the peptide segments in the polymers. They can be enlarged by lowering pH from 10 to 5, thus allowing complete removal of the template protein under mild conditions. When the pH is adjusted back to 10, their original size and shape will be recovered. Therefore, the MIP binds the template protein BHb with high affinity. Compared with the MIP crosslinked with the commonly used crosslinker, the imprinting efficiency of the PC-crosslinked MIP is significantly improved. In addition, both the maximum adsorption capacity (641.9 mg/g) and imprinting factor (7.2) are much higher than the BHb MIPs reported previously. The new BHb MIP also exhibits high selectivity toward BHb and good reusability. Thanks to the high adsorption capacity and high selectivity of the MIP, when it was applied to extract BHb from bovine blood, BHb in the blood sample was extracted almost completely, and high purity product was obtained.

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Section: Results and Discussionmentioning

confidence: 99%

Molecularly Imprinted Polymers with Shape-Memorable Imprint Cavities for Efficient Separation of Hemoglobin from Blood

Dong

Guan

et al. 2023

Biomacromolecules

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“…Molecular simulation of PEGylated bovine serum albumin (BSA) revealed the correlation between the molecular weight of the attached PEG and the shelf life of BSA . In addition to PEG, researchers have explored a wide range of attached partners, including zwitterionic polymers, , glycopolymers, oligo-EGylated poly(meth)acrylates, , and intrinsically disordered peptides. , The flexible and unstructured conformation is the common characteristic of all these polymers, which is believed to be entropically unfavored in biofouling events …”

Section: Introductionmentioning

confidence: 99%

“…For most polymers, it is necessary to change their chemical composition for obtaining different conformation, and vice versa. Recently, the Lu group synthesized a series of poly(amino acid)s with helical or unstructured conformations just by changing the chirality of residues. In particular, the homopolymerization of l -/ d -glutamate derivatives containing oligoethylene glycol (i.e., EG 3 ) as side chains may form helical structures.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 The flexible and unstructured conformation is the common characteristic of all these polymers, which is believed to be entropically unfavored in biofouling events. 14 However, such an assumption that the coiled polymers perform better lacks solid experimental evidence. It is difficult to experimentally set up a rational control group in which the conjugated polymer analogs show different conformations but share the same chemical composition.…”

Section: ■ Introductionmentioning

confidence: 99%

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Molecular Insights into the Improved Bioactivity of Interferon Conjugates Attached to a Helical Polyglutamate

et al. 2023

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Attaching polymers, especially polyethylene glycol (PEG), to protein drugs has emerged as a successful strategy to prolong circulation time in the bloodstream. The hypothesis is that the flexible chain wobbles on the protein's surface, thus resisting potential nonspecific adsorption. Such a theoretical framework may be challenged when a helical polyglutamate is used to conjugate with target proteins. In this study, we investigated the structure−activity relationships of polyglutamate-interferon conjugates P(EG 3 Glu)-IFN using molecular simulations. Our results show that the local crowding effect induced by oligoethylene glycols (i.e., EG 3 ) is the primary driving force for helix formation in P(EG 3 Glu), and its helicity can be effectively increased by reducing the free volume of the two termini. Furthermore, it was found that the steric hindrance induced by IFN is not conductive to the helicity of P(EG 3 Glu) but contributes to its dominant orientation relative to interferon. The orientation of IFN relative to the helical P(EG 3 Glu) can help to protect the protein drug from neutralizing antibodies while maintaining its bioactivity. These findings suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein−polymer conjugates.

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“…However, these approaches have been limited by the inherent immunogenicity of carriers and ambiguous components in synthetic carriers involving a variety of reactions . Synthesized peptides have emerged to address these limitations, which possess several advantages including controllable self-assembled formulation, stable physicochemical properties, etc. − With rational design of the peptide sequences, peptide antigens can self-assemble into well-defined structures with integration of multiepitope peptides but no other delivery vectors, which may elicit a broad spectrum of immune responses and substantially potentiate the efficacy of subunit vaccines.…”

mentioning

confidence: 99%

Nanovaccine Based on a Biepitope Antigen to Potentiate the Immunogenicity of a Neoantigen

Chen

Zhang

et al. 2023

ACS Macro Lett.

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Specific neoantigens are promising candidates for personalized cancer vaccines and immunotherapies, whereas the low immunogenicity and physicochemical variability are the main challenges in clinical trials. Herein, based on the rational design of neoantigens, we developed biepitope nanovaccines via integrating CD4+ with CD8+ T cell epitopes. A class of amphiphilic peptides composed of biepitope and hydrophilic amino acids can form well-defined nanostructures, thus incorporating functional sequences into an artificial platform. Cellular uptake studies demonstrated the enhanced endocytosis of biepitope neoantigens in dendritic cells (DCs). Such designed biepitopes can further stimulate the maturation of DCs, as validated by the upregulation of costimulatory molecules and secreted proinflammatory cytokines, which show the potential ability to prime T cells and evoke specific cellular immunity. The inspiring prophylactic and therapeutic efficacy of biepitope nanovaccines was evaluated in murine colon cancer. In contrast to individual CD8+ T cell epitopes, the rationally designed biepitope nanovaccines can efficiently provoke immune activation and potentiate antitumor immunity both in vitro and in vivo, presenting an alternative strategy for neoantigen vaccines.

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Helical Nonfouling Polypeptides for Biomedical Applications

Cited by 8 publications

References 182 publications

Molecularly Imprinted Polymers with Shape-Memorable Imprint Cavities for Efficient Separation of Hemoglobin from Blood

Molecularly Imprinted Polymers with Shape-Memorable Imprint Cavities for Efficient Separation of Hemoglobin from Blood

Molecular Insights into the Improved Bioactivity of Interferon Conjugates Attached to a Helical Polyglutamate

Nanovaccine Based on a Biepitope Antigen to Potentiate the Immunogenicity of a Neoantigen

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