Expanding peptide-cucurbit[7]uril interactions through selective N-terminal reductive alkylation

Meudom, Rolande; Zheng, Nan; Zhu, Shugao; Jacobsen, Michael T.; Cao, Liping; Chou, Danny Hung‐Chieh

doi:10.1016/j.crchbi.2021.100013

Cited by 5 publications

(5 citation statements)

References 40 publications

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“…Because hCT lacks a terminal Phe for host−guest complexation, the N-terminal amine was selectively modified on-resin with a benzylic amine group using reductive amination chemistry (Figure 3B). 44 To optimize binding, two spacer lengths between the terminal amine and the benzyl ring were examined comprising either one or two methylene units (hCT A1 and A2, respectively). We examined aggregation behavior over 40 h using the methods previously described and with or without CB [7]-PMet CM 80 .…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…We selected hCT (Figure A) as another model protein therapeutic. Because hCT lacks a terminal Phe for host–guest complexation, the N-terminal amine was selectively modified on-resin with a benzylic amine group using reductive amination chemistry (Figure B) . To optimize binding, two spacer lengths between the terminal amine and the benzyl ring were examined comprising either one or two methylene units (hCT A1 and A2, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…Aggregation Assays. Peptide therapeutics were prepared 44 and aggregation was assessed 7,17 using previously published methods. Insulin or calcitonin solutions were prepared in phosphate-buffered saline (PBS) at pH = 7.4 at a final concentration of 1 mg/mL or 0.5 mg/mL respectively, and with and without the addition of 1.5 molar equiv of CB [7]-PMet for recombinant human (rHu) insulin and 5 molar equiv for human calcitonin (hCT).…”

Section: Preparation Of Cb[7] Functional Poly(l-methionine)mentioning

confidence: 99%

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Supramolecular Protein Stabilization with Zwitterionic Polypeptide–Cucurbit[7]uril Conjugates

Clauss

Meudom

et al. 2022

Biomacromolecules

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Protein aggregation is an obstacle for the development of new biopharmaceuticals, presenting challenges in shipping and storage of vital therapies. Though a variety of materials and methods have been explored, the need remains for a simple material that is biodegradable, nontoxic, and highly efficient at stabilizing protein therapeutics. In this work, we investigated zwitterionic polypeptides prepared using a rapid and scalable polymerization technique and conjugated to a supramolecular macrocycle host, cucurbit[7]uril, for the ability to inhibit aggregation of model protein therapeutics insulin and calcitonin. The polypeptides are based on the natural amino acid methionine, and zwitterion sulfonium modifications were compared to analogous cationic and neutral structures. Each polymer was end-modified with a single cucurbit[7]uril macrocycle to afford supramolecular recognition and binding to terminal aromatic amino acids on proteins. Only conjugates prepared from zwitterionic structures of sufficient chain lengths were efficient inhibitors of insulin aggregation and could also inhibit aggregation of calcitonin. This polypeptide exhibited no cytotoxicity in human cells even at concentrations that were five-fold of the intended therapeutic regime. We explored treatment of the zwitterionic polypeptides with a panel of natural proteases and found steady biodegradation as expected, supporting eventual clearance when used as a protein formulation additive.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Preparation Of Cb[7] Functional Poly(l-methionine)mentioning

confidence: 99%

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Supramolecular Protein Stabilization with Zwitterionic Polypeptide–Cucurbit[7]uril Conjugates

Clauss

Meudom

et al. 2022

Biomacromolecules

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“…The diversified ligands on the surfaces of the nanocluster are bounded up with the ECL property of AuNCs and enhance the binding capacity for incorporating other materials. Through the host and guest recognition between CB [7] and L-Phe, 32,33 CB [7] selfassembles on the surface of the AuNCs to harden the nanocluster. As a result, the ECL efficiency of CB [7]/L-Phe/ MPA-AuNCs was up to 3.4% in aqueous solutions, while the AuNCs without host−guest recognition exhibited poor stability and relatively low ECL efficiency under the same conditions.…”

Section: ■ Introductionmentioning

confidence: 99%

Cucurbituril Enhanced Electrochemiluminescence of Gold Nanoclusters via Host–Guest Recognition for Sensitive D-Dimer Sensing

et al. 2022

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Gold nanoclusters (AuNCs) are promising electrochemiluminescence (ECL) signal probes for their outstanding biocompatibility, unusual molecule-like structures, and versatile optical and electrochemical properties. Nevertheless, their relatively low ECL efficiency and poor stability in aqueous solutions hindered their application in the ECL sensing field. Herein, a facile host−guest recognition strategy was proposed to enhance the ECL efficiency and stability of Au NCs by rigidifying the surface of ligand-stabilized AuNCs via supramolecular self-assembly between cucurbiturils[7] (CB [7]) and L-phenylalanine (L-Phe). Meanwhile, mercaptopropionic acid (MPA) was introduced as a ligand in order to cooperatively enhance the performance of the AuNCs and facilitate the link between AuNCs and bioactive substances. The prepared CB[7]/L-Phe/MPA-AuNCs had a higher ECL emission efficiency, achieving about 2-fold stronger ECL intensity than that of L-Phe/MPA-AuNCs. In addition, after non-covalent modification with CB[7], the finite stability of the papered AuNCs was significantly improved. The prepared CB[7]/L-Phe/MPA-AuNCs showed excellent D-dimer sensing results, exhibiting a linear range from 50.00 fg/mL to 100.0 ng/mL and a detection limit of 29.20 fg/mL (S/N = 3). Our work demonstrated that the host−guest self-assembly strategy provided a universal approach for strengthening the ECL efficiency and stability of nanostructures on an ultra-small scale.

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“…3,4 Ultra-high host-guest binding affinities in water are key for biological applications, for example in pull-down assays, stabilization of biopharmaceuticals, and bioimaging. 3,5 Within recent years, attempts have been made to identify peptide binding epitopes with a strong affinity to CBs, in particular to the highly water-soluble homologue cucurbit [7]uril (CB7), which included sequences of naturally occurring, proteinogenic amino acids, 6 as well as artificial binding epitopes 7 and noncanonical amino acids. 2,[8][9][10] Stable CB7 complexes with noncanonical amino acids were first explored by Urbach and co-workers and included the p-tertbutyl and p-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe, Fig.…”

mentioning

confidence: 99%

Adamantylglycine as a high-affinity peptide label for membrane transport monitoring and regulation

Pramod,

Alnajjar,

Schöpper

et al. 2024

Chem. Commun.

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Expanding peptide-cucurbit[7]uril interactions through selective N-terminal reductive alkylation

Cited by 5 publications

References 40 publications

Supramolecular Protein Stabilization with Zwitterionic Polypeptide–Cucurbit[7]uril Conjugates

Supramolecular Protein Stabilization with Zwitterionic Polypeptide–Cucurbit[7]uril Conjugates

Cucurbituril Enhanced Electrochemiluminescence of Gold Nanoclusters via Host–Guest Recognition for Sensitive D-Dimer Sensing

Adamantylglycine as a high-affinity peptide label for membrane transport monitoring and regulation

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