12 research outputs found
Enzyme-Catalyzed Macrocyclization of Long Unprotected Peptides
A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective SNAr reaction between an N-terminal glutathione (GSH, γ-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quantitatively produced within 2 h in aqueous pH = 8 buffer at room temperature. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chemical ligation to generate a large 40-residue peptide macrocycle.Massachusetts Institute of Technology (MIT startup funds)National Institutes of Health (U.S.) (grant GM101762)Damon Runyon Cancer Research Foundation (Award)Sontag Foundation (Distinguished Scientist Award)Amgen Inc. (Summer Graduate Research Fellowship
Entwicklung eines flexiblen synthetischen Zugangs zu α-Helix-Peptid-Mimetika auf der Basis von Terphenylen zur Inhibierung von Protein-Protein-Wechselwirkungen
A Modular Synthesis of Teraryl-Based α-Helix Mimetics, Part1: Synthesis of Core Fragments with Two Electronically Differentiated Leaving Groups
A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger-mediated ring closure
Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing alpha-, beta- or gamma-amino acid residues is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and tripeptides - recognized as difficult targets - were obtained in moderate to good yields according to a straightforward sequence. Empirical force-field calculations were undertaken to determine their conformational behaviors and showed high levels of similarity with X-ray results. A computational study at the B3LYP/6-31+G** level of theory afforded information regarding the impact of the sequence, ring-size and substitution on the activation barriers for the cyclization of azido peptide thioesters
Reactivity of Electrochemically Generated Rhenium (II) Tricarbonyl α-Diimine Complexes: A Reinvestigation of the Oxidation of Luminescent Re(CO)3(α-Diimine)Cl and Related Compounds
The oxidative electrochemistry of luminescent rhenium (I) complexes of the type Re(CO)3(LL)Cl, 1, and Re(CO)3(LL)Br, 2, where LL is an α-diimine, was re-examined in acetonitrile. These compounds undergo metal-based one-electron oxidations, the products of which undergo rapid chemical reaction. Cyclic voltammetry results imply that the electrogenerated rhenium (II) species 1+ and 2+ disproportionate, yielding [Re(CO)3(LL)(CH3CN)]+, 7, and additional products. Double potential step chronocoulometry experiments confirm that 1+ and 2+ react via second-order processes and, furthermore, indicate that the rate of disproportionation is influenced by the basicity and steric requirements of the α-diimine ligands. The simultaneous generation of rhenium (I) and (III) carbonyl products was detected upon the bulk oxidation of 1 using infrared spectroelectrochemistry. The rhenium (III) products are assigned as [Re(CO)3(LL)Cl2]+, 5; an inner-sphere electron-transfer mechanism of the disproportionation is proposed on the basis of the apparent chloride transfer. Chemically irreversible two-electron reduction of 5 yields 1 and Cl−. No direct spectroscopic evidence was obtained for the generation of rhenium (III) tricarbonyl bromide disproportionation products, [Re(CO)3(LL)Br2]+, 6; this is attributed to their relatively rapid decomposition to 7 and dibromine. In addition, the 17-electron radical cations, 7+, were successfully characterized using infrared spectroelectrochemistry