142650-55-3Relevant articles and documents
Macrocyclic Modalities Combining Peptide Epitopes and Natural Product Fragments
Carbajo, Rodrigo J.,Grossmann, Tom N.,Larsson, Niklas,Lemurell, Malin,Plowright, Alleyn T.,Potowski, Marco,Thavam, Sasikala,Valeur, Eric,Waldmann, Herbert,Dahl, G?ran,Dellsén, Anita,Guéret, Stéphanie M.
supporting information, p. 4904 - 4915 (2020/04/01)
"Hot loop" protein segments have variable structure and conformation and contribute crucially to protein-protein interactions. We describe a new hot loop mimicking modality, termed PepNats, in which natural product (NP)-inspired structures are incorporated as conformation-determining and-restricting structural elements into macrocyclic hot loop-derived peptides. Macrocyclic PepNats representing hot loops of inducible nitric oxide synthase (iNOS) and human agouti-related protein (AGRP) were synthesized on solid support employing macrocyclization by imine formation and subsequent stereoselective 1,3-dipolar cycloaddition as key steps. PepNats derived from the iNOS DINNN hot loop and the AGRP RFF hot spot sequence yielded novel and potent ligands of the SPRY domain-containing SOCS box protein 2 (SPSB2) that binds to iNOS, and selective ligands for AGRP-binding melanocortin (MC) receptors. NP-inspired fragment absolute configuration determines the conformation of the peptide part responsible for binding. These results demonstrate that combination of NP-inspired scaffolds with peptidic epitopes enables identification of novel hot loop mimics with conformationally constrained and biologically relevant structure.
Synthesis of Albicidin Derivatives: Assessing the Role of N-terminal Acylation on the Antibacterial Activity
Kerwat, Dennis,Gr?tz, Stefan,Kretz, Julian,Seidel, Maria,Kunert, Maria,Weston, John B.,Süssmuth, Roderich D.
supporting information, p. 1899 - 1903 (2016/10/12)
The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium, Xanthomonas albilineans, represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram-positive and Gram-negative microorganisms. Its unique structure potentially represents a new lead structure for the development of an antibacterial drug. Here we report the synthesis of 14 albicidin derivatives with structural variations at the N-terminus, primarily investigating the effects of variation of cinnamoyl, phenylpropanoyl, and benzoyl residues. Gyrase inhibition in vitro and determination of minimal inhibitory concentrations were assessed in parallel. Activities in a nanomolar range and the importance of N-acylation were demonstrated.
Development of a new nonpeptidic self-immolative spacer. application to the design of protease sensing fluorogenic probes
Meyer, Yves,Richard, Jean-Alexandre,Massonneau, Marc,Renard, Pierre-Yves,Romieu, Anthony
supporting information; experimental part, p. 1517 - 1520 (2009/04/18)
The design and synthesis of novel self-immolative spacer systems aiming at the release of phenol-containing compounds are described. The newly designed traceless linkers proved to be conveniently stable under physiological conditions and operate through spontaneous decomposition of an hemithioaminal intermediate under neutral aqueous conditions. Their utility was then illustrated by the preparation of original fluorogenic substrates of penicillin amidase whose strong fluorescence is unveiled through enzyme-initiated domino reactions.
