Rapid and Highly Productive Assembly of a Disulfide Bond in Solid-Phase Peptide Macrocyclization.

Org Lett

Biomimetic Peptide Engineering Lab, Department of Chemistry, Indian Institute of Technology Ropar, Baraphool, Rupnagar, Punjab, India 140001.

Published: March 2023

Here we report a highly efficient disulfide-driven peptide macrocyclization in 15 min on a solid support using persulfate as a crucial additive in iodine-mediated oxidative cyclization. The method eliminates the side products of classical iodine-mediated peptide cyclization. It is operationally simple and convenient for cyclizing small to lengthier peptides embodying popular cysteine building blocks in a single step.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.3c00078DOI Listing

Publication Analysis

Top Keywords

peptide macrocyclization
8
rapid highly
4
highly productive
4
productive assembly
4
assembly disulfide
4
disulfide bond
4
bond solid-phase
4
solid-phase peptide
4
macrocyclization report
4
report highly
4

Similar Publications

Peptide-Bismuth Tricycles: Maximizing Stability by Constraint.

Chemistry

January 2025

Australian National University, Research School of Chemistry, Sullivans Creek Road, ACT 2601, Canberra, AUSTRALIA.

Constrained peptides possess excellent properties for identifying lead compounds in drug discovery. While it has become increasingly straightforward to discover selective high-affinity peptide ligands, especially through genetically encoded libraries, their stability and bioavailability remain significant challenges. By integrating macrocyclization chemistry with bismuth binding, we generated series of linear, cyclic, bicyclic, and tricyclic peptides with identical sequences.

View Article and Find Full Text PDF

Late-Stage Stitching Enabled by Palladium-Catalyzed Tryptophan C4 Amination: Peptide Ligation and Cyclodimerization.

Org Lett

January 2025

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.

Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp)-H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C-N bonds, facilitating the construction of cyclopeptides via late-stage cyclodimerization of structurally complex peptides, which poses significant challenges for organic synthesis. The synthetic utility of this protocol is demonstrated through the synthesis of 30- to 38-membered macrocyclic peptides.

View Article and Find Full Text PDF

Background: The biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.

View Article and Find Full Text PDF

Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed αβ integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)-Mito-MIMs-TPP are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy.

View Article and Find Full Text PDF

Molecular and biochemical evolution of casbene-type diterpene and sesquiterpene biosynthesis in rice.

J Integr Plant Biol

January 2025

National Key Laboratory for Tropical Crop Breeding, School of Breeding and Multiplication (Sanya Institute of Breeding and Multiplication), Hainan University, Sanya, 572025, China.

Casbene and neocembrene are casbene-type macrocyclic diterpenes; their derivatives play significant roles in plant defense and have pharmaceutical applications. We had previously characterized a casbene synthase, TERPENE SYNTHASE 28 (OsTPS28), in rice (Oryza sativa). However, the mechanism of neocembrene biosynthesis in rice remained unclear.

View Article and Find Full Text PDF

Want 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!