A versatile and rapid synthetic strategy has been developed for the on-resin cyclization of peptides using thiol-ene photochemistry. This unique method exploits the thiol group of natural cysteine amino acids and allows for various alkenes to be incorporated orthogonal to the peptide backbone.
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http://dx.doi.org/10.1039/c001375g | DOI Listing |
Biomacromolecules
January 2025
DISFARM, Department of Pharmaceutical Sciences, "A. Marchesini" General and Organic Chemistry Section, Università degli Studi di Milano, Via Venezian 21, Milan 20133, Italy.
In nature, organisms living in extreme environmental conditions produce antifreeze proteins (AFPs) that prevent the growth of ice crystals and depress the freezing point of body fluids. In this study, three different peptides derived from the N-terminal sequence of the helical type I AFP HPLC6, along with a stapled derivative produced via on-resin microwave-assisted copper(I)-catalyzed azide-alkyne cycloaddition, were conjugated to gold nanoparticles. The aim of decorating the surface of the nanoparticles with multiple copies of the peptides was to combine the ice-binding capability of the peptides with the size of a nanoparticle, thus, mimicking the protein bulkiness to enhance the peptide antifreeze activity.
View Article and Find Full Text PDFJ Org Chem
January 2025
RayzeBio, Inc, 5505 Morehouse Drive, Suite 300, San Diego, California 92121, United States.
The standard protocol for Alloc group removal during peptide synthesis still presents limitations, including low reaction yields, -allylated byproducts, and the use of air-sensitive Pd(PPh). We addressed these challenges by developing a novel protocol using the air-stable Pd(PPh)Cl catalyst, Meldrum's acid (MA), and triethylsilane (TES-H). This combination ensured high yields, eliminated -allylated byproducts, and is compatible with automated synthesis.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany.
Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone anti-proliferative activity against human cancer cells, which resulted in IC values in the nanomolar range.
View Article and Find Full Text PDFProtein Expr Purif
February 2025
School of Life Science, Anhui Agricultural University, Hefei, Anhui, 230036, PR China. Electronic address:
Previously, we identified the human annexin A1 as a purification tag for column-free purification with gentler calcium-responsive precipitation. In this work, we used the annexin A1 tagged green fluorescent protein constructs for detecting extracellular production in Escherichia coli, Bacillus subtilis, and Pichia pastoris, and identified that the leaderless fusion protein was transported extracellularly in E. coli with supply of additives including Triton X-100.
View Article and Find Full Text PDFChemistry
December 2024
Dipartimento di Scienze Farmaceutiche, Sez. Chimica Generale e Organica A. Marchesini, Università degli Studi di Milano, Via Venezian 21, 20133, Milan, Italy.
Nowadays, peptidomimetics are widely studied, being useful tools in drug discovery and medicinal chemistry. The coupling between a carboxylic acid with an amine to form a peptide bond is the most common reaction to obtain peptides/peptidomimetics. In this work, we have investigated an innovative metal-free photoredox-catalyzed carbamoylation to form peptidomimetics thanks to the reaction between dihydropyridines functionalized with amino acids (or peptide sequences) and differently functionalized imines.
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