Herein we report the Ru(II)-catalyzed double-macrocyclization of a hexapeptide to obtain a mimic of the bicyclic CDE-ring of vancomycin, followed by measurement of its binding affinity for small peptide ligands using ITC.

The partial positive charge of amide protons is used to promote macrocyclization and form crown-ether analogs. Their deprotonation generates very selective pH-switchable alkaline earth ion receptors only in the presence of an appropriate substrate.

A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and intramolecular nucleophiles. Reactions are performed in aqueous media, in the absence of side chain protecting groups...

Macrocycles are key structural elements in numerous bioactive small molecules and are attractive targets in the diversity-oriented synthesis of natural product-based libraries. However, efficient and systematic access to diverse collections of macrocycles has proven difficult using classical macrocyclization reactions. To address this problem, we have developed a concise, modular approach to th...

We report here, for the first time, the BOP-mediated one-pot macrocyclization that is facilitated and guided by internally placed intramolecular H-bonds to allow for the highly selective formation of five-residue cation-binding macrocycles.

The Cover Feature shows a chiral sulfinyl auxiliary in the ortho-position of biaryl axis inducing C–H activated atroposelective macrocyclization with final transformation to configurationally stable natural Isoriccardin C. More information can be found Communication by S. Choppin, A. Speicher et al.

Macrocyclization of a peptide or a lipopeptide occurs at the last step of synthesis and is usually catalyzed by a single C-terminal thioesterase (Te) domain. Arthrofactin synthetase (Arf) from Pseudomonas sp. MIS38 represents a novel type of nonribosomal peptide synthetase that contains unique tandem C-terminal Te domains, ArfC_Te1 and ArfC_Te2. In order to analyze their function in vivo, site-...

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a uniq...

Macrocycles are commonly synthesized via late-stage macrolactamization and macrolactonization. Strategies involving C–C bond macrocyclization have been reported, examples include the transition-metal-catalyzed ring-closing metathesis coupling reactions. In this mini-review, we summarize recent progress in direct synthesis of polyketide polypeptide macrocycles using a C–H activation strategy. fi...

Bottromycin A2 is a structurally unique ribosomally synthesized and post-translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug-resistant bacteria. The structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare β-methylated amino acid residues. The N-terminus of a precursor peptide (BtmD) is converted into bottromy...