Orexin receptors in GtoPdb v.2021.3

Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Orexin receptors [42]) are activated by the endogenous polypeptides orexin-A and orexin-B (also known as hypocretin-1 and -2; 33 and 28 aa) derived from a common precursor, preproorexin or orexin precursor, by proteolytic cleavage and some typical peptide modifications [109]. Currently the only orexin receptor ligands in clinical use are suvorexant and lemborexant, which are used as hypnotics. Orexin receptor crystal structures have been solved [134, 133, 54, 117, 46].

Leader peptide exchange to produce hybrid, new-to-nature ribosomal natural products

Ribosomal natural products contain exquisite post-translational peptide modifications that are installed by a range of pathway-specific enzymes. We present proof of principle for a Sortase A-based approach that enables peptide...

DNAzymes for Amine and Peptide Lysine Acylation

DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However, finding DNAzymes for peptide lysine acylation is a substantial challenge. By using suitably reactive aryl ester acyl donors as the electrophiles, here we used in vitro selection to identify DNAzymes that acylate amines, including lysine side chains of DNA-anchored peptides. Some of the DNAzymes can transfer a small glutaryl group to an amino group. These results expand the scope of DNAzyme catalysis and suggest the future broader applicability of DNAzymes for sequence-selective lysine acylation of peptide and protein substrates.

DNAzymes for Amine and Peptide Lysine Acylation

DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However, finding DNAzymes for peptide lysine acylation is a substantial challenge. By using suitably reactive aryl ester acyl donors as the electrophiles, here we used in vitro selection to identify DNAzymes that acylate amines, including lysine side chains of DNA-anchored peptides. Some of the DNAzymes can transfer a small glutaryl group to an amino group. These results expand the scope of DNAzyme catalysis and suggest the future broader applicability of DNAzymes for sequence-selective lysine acylation of peptide and protein substrates.

DrawGlycan-SNFG and gpAnnotate: rendering glycans and annotating glycopeptide mass spectra

Summary This manuscript describes an open-source program, DrawGlycan-SNFG (version 2), that accepts IUPAC (International Union of Pure and Applied Chemist)-condensed inputs to render Symbol Nomenclature For Glycans (SNFG) drawings. A wide range of local and global options enable display of various glycan/peptide modifications including bond breakages, adducts, repeat structures, ambiguous identifications etc. These facilities make DrawGlycan-SNFG ideal for integration into various glycoinformatics software, including glycomics and glycoproteomics mass spectrometry (MS) applications. As a demonstration of such usage, we incorporated DrawGlycan-SNFG into gpAnnotate, a standalone application to score and annotate individual MS/MS glycopeptide spectrum in different fragmentation modes. Availability and implementation DrawGlycan-SNFG and gpAnnotate are platform independent. While originally coded using MATLAB, compiled packages are also provided to enable DrawGlycan-SNFG implementation in Python and Java. All programs are available from https://virtualglycome.org/drawglycan; https://virtualglycome.org/gpAnnotate. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

Orexin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Orexin receptors [39]) are activated by the endogenous polypeptides orexin-A and orexin-B (also known as hypocretin-1 and -2; 33 and 28 aa) derived from a common precursor, preproorexin or orexin precursor, by proteolytic cleavage and some typical peptide modifications [102]. Currently the only orexin receptor ligand in clinical use is suvorexant, which is used as a hypnotic. Orexin receptor crystal structures have been solved [124, 123].

Peptide Modifications: Versatile Tools in Peptide and Natural Product Syntheses

Peptide modifications via C–C bond formation have emerged as valuable tools for the preparation and alteration of non-proteinogenic amino acids and the corresponding peptides. Modification of glycine subunits in peptides allows for the incorporation of unusual side chains, often in a highly stereoselective manner, orchestrated by the chiral peptide backbone. Moreover, modifications of peptides are not limited to the peptidic backbone. Many side-chain modifications, not only by variation of existing functional groups, but also by C–H functionalization, have been developed over the past decade. This account highlights the synthetic contributions made by our group and others to the field of peptide modifications and their application in natural product syntheses.1 Introduction2 Peptide Backbone Modifications via Peptide Enolates2.1 Chelate Enolate Claisen Rearrangements2.2 Allylic Alkylations2.3 Miscellaneous Modifications3 Side-Chain Modifications3.1 C–H Activation3.1.1 Functionalization via Csp3–H Bond Activation3.2.2 Functionalization via Csp2–H Bond Activation3.2 On Peptide Tryptophan Syntheses4 Conclusion