Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643349 | PMC |
| http://dx.doi.org/10.1038/s41598-022-23481-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Late-Stage Fluorination of Tyrosine Residues in Antiviral Protein Cyanovirin-N.
Chem Asian J
December 2024
Instituto de Pesquisas de Produtos Naturais Walter Mors, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil.
The applications of fluorinated molecules in chemical biology are rapidly expanding driven by the unique properties of C-F bonds, leading to increased interest in methodologies for controlled introduction of this atom. In this study, we present the first method for late-stage fluorination of tyrosine residues in proteins. Our results demonstrate that electrophilic fluorination using Selectfluor, a stable and non-toxic reagent, offers a straightforward and cost-effective method for labeling Cyanovirin-N (CVN), a 101-amino-acid lectin with effective antiviral activity.
View Article and Find Full Text PDFAmyloid β-Peptide Segment Conjugated Side-Chain Proline-Based Polymers as Potent Inhibitors in Lysozyme Amyloidosis.
Bioconjug Chem
March 2024
Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, Nadia, West Bengal 741246, India.
Developing effective amyloidosis inhibitors poses a significant challenge due to the dynamic nature of the protein structures, the complex interplay of interfaces in protein-protein interactions, and the irreversible nature of amyloid assembly. The interactions of amyloidogenic polypeptides with other peptides play a pivotal role in modulating amyloidosis and fibril formation. This study presents a novel approach for designing and synthesizing amyloid interaction surfaces using segments derived from the amyloid-promoting sequence of amyloid β-peptide [VF(Aβ(18-19)/FF(Aβ(19-20)/LVF(Aβ(17-19)/LVFF(Aβ(17-20)], where VF, FF, LVF and LVFF stands for valine phenylalanine dipeptide, phenylalanine phenylalanine dipeptide, leucine valine phenylalanine tripeptide and leucine valine phenylalanine phenylalanine tetrapeptide, respectively.
View Article and Find Full Text PDFA computational insight on the aromatic amino acids conjugation with [Cp*Rh(HO)] by using the meta-dynamics/FMO3 approach.
J Mol Model
December 2023
Department of Pharmacy, Università "G. D'Annunzio" Di Chieti-Pescara, I-66100, Chieti, Italy.
Context: Rh(III) complexes demonstrated to exert promising pharmacological effects with potential applications as anti-cancer, anti-bacterial, and antimicrobial agents. One important Rh(III)-ligand is the pentamethylcyclopentadienyl (Cp*) group forming in water the [Cp*Rh(HO)] complex. Among of its attractive chemical properties is the ability to react specifically with Tyr amino acid side chain of G-protein-coupled receptor (GPCR) peptides by means of highly chemoselective bioconjugation reaction, at room temperature and at pH 5-6.
View Article and Find Full Text PDFEngineering E2 Bionanoparticles for Targeted Delivery of Chemotherapeutics to Breast Cancer Cells.
Methods Mol Biol
January 2024
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
Naturally occurring protein nanocages are promising drug carriers as both the interior and exterior can be decorated for drug encapsulation and cell targeting. To provide surface functionalization, we added a SpyTag to E2 nanocages (ST-E2) to enable tunable decoration using the robust SpyCatcher bioconjugation strategy. Additionally, the E2 core was mutated with four phenylalanine substitutions for doxorubicin loading and pH-responsive release.
View Article and Find Full Text PDFEncoding Noncanonical Amino Acids into Phage Displayed Proteins.
Methods Mol Biol
June 2023
Institut Químic de Sarrià (IQS), Universitat Ramon Llull, Barcelona, Spain.
Phage display facilitates the evolution of peptides and proteins for affinity selection against targets, but it is mostly limited to the chemical diversity provided by the naturally encoded amino acids. The combination of phage display with genetic code expansion allows the incorporation of noncanonical amino acids (ncAAs) into proteins expressed on the phage. In this method, we describe incorporation of one or two ncAAs in a single-chain fragment variable (scFv) antibody in response to amber or quadruplet codon.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!