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The development and application of commercially available automated peptide synthesizers has played an essential role in almost all areas of peptide and protein research. Recent advances in peptide synthesis method and solid-phase chemistry provide new opportunities for optimizing synthetic efficiency of peptide synthesizers. The efforts in this direction have led to the successful preparation of peptides up to more than 150 amino acid residues in length. Such success is particularly useful for addressing the challenges associated with the chemical synthesis of glycoproteins. The purpose of this review is to provide a brief overview of the evolution of peptide synthesizer and glycoprotein synthesis. The discussions in this article include the principles underlying the representative synthesizers, the strengths and weaknesses of different synthesizers in light of their principles, and how to further improve the applicability of peptide synthesizers in glycoprotein synthesis.
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http://dx.doi.org/10.3389/fchem.2022.896098 | DOI Listing |
J Am Chem Soc
September 2025
Center for Chemical Glycobiology, Shanghai Key Laboratory for Antibody-Drug Conjugates with Innovative Target, State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
The ability to selectively cleave C-heteroatom bonds is critically important in chemical science, from peptide and protein synthesis to biomolecule manipulation. For example, C-heteroatom bond cleavage is widely used in fluorenylmethyloxycarbonyl/-butyl (Fmoc/Bu)-based solid-phase peptide synthesis (SPPS). Despite its usefulness, it has inextricable limitations, such as issues with hydrophobicity and side reactions, owing to the need for the use of a strong trifluoroacetic acid (TFA, a pervasive forever chemical) as the cleavage reagent.
View Article and Find Full Text PDFNat Chem
August 2025
State Key Laboratory of Coordination Chemistry, and Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Incorporating unnatural amino acids, such as hindered N-methylated or α,α-disubstituted amino acid(s), into peptides can improve their properties for application in the pharmaceutical and biomedical fields. However, the current solid-phase peptide synthesis (SPPS) faces sluggish reaction rates and low yields when incorporating sterically hindered amino acids, owing to the poor kinetics of the two-phase acyl-transfer process from solution to solid. Here we introduce an immobilized ribosome-mimicking molecular reactor to facilitate on-resin proximity-induced intra(inter)-reactor acyl transfers.
View Article and Find Full Text PDFInt J Nanomedicine
July 2025
Department of Otolaryngology, Head and Neck Surgery, Rush University Medical Center, Chicago, IL, 60612, USA.
Aim: Otitis media is a common otolaryngologic diagnosis worldwide. Invasive methods to curtail and treat frequent occurrences are undesirable, thus necessitating the identification and production of a non-invasive approach to treating the disease. Due to tympanic membrane thickness, ototopical drug delivery is challenging.
View Article and Find Full Text PDFJ Org Chem
June 2025
Department of Molecular Biochemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Backbone N-methylation is a pivotal peptide modification that enhances lipophilicity, metabolic stability, and binding affinity or specificity, thereby improving bioactive peptides' bioavailability. Substitution of a backbone amide hydrogen with a methyl group is a three-step procedure which is fully integrated with solid-phase peptide synthesis strategy and usually takes about 4 h. We have revolutionized this process by optimizing the method and slashing the total N-methylation procedure time from 4 h to just 40 min.
View Article and Find Full Text PDFMethods Mol Biol
April 2025
Indian Institute of Science Education and Research, Pune, India.
Amphiphilic glycopeptides and glycopolymers have been characterized as potential glycocalyx engineering probes to regulate growth factors mediated stem cell differentiation and neural plasticity. Here, we describe a rational and facile method to synthesize fluorescent tagged amphiphilic multivalent glycoprobes using solid-phase peptide synthesizer and copper-free click chemistry. As a prototype, we report the synthesis of fluorescently tagged penta-valent sulfated L-iduronic acid glycopeptide for cell surface engineering and imaging.
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