Christopher J. White

Bio: Christopher J. White is an academic researcher from University of Toronto. The author has contributed to research in topics: Peptide & Peptide Conformation. The author has an hindex of 7, co-authored 10 publications receiving 932 citations. Previous affiliations of Christopher J. White include ETH Zurich.

Contemporary strategies for peptide macrocyclization

Abstract: Peptide macrocycles have found applications that range from drug discovery to nanomaterials. These ring-shaped molecules have shown remarkable capacity for functional fine-tuning. Such capacity is enabled by the possibility of adjusting the peptide conformation using the techniques of chemical synthesis. Cyclic peptides have been difficult, and often impossible, to prepare using traditional synthetic methods. For macrocyclization to occur, the activated peptide must adopt an entropically disfavoured pre-cyclization conformation before forming the desired product. Here, we review recent solutions to some of the major challenges in this important area of contemporary synthesis.

Management of Bell palsy: clinical practice guideline

Abstract: Bell palsy is an idiopathic weakness or paralysis of the face of peripheral nerve origin, with acute onset. It affects 20–30 persons per 100 000 annually, and 1 in 60 individuals will be affected over the course of their lifetime.[1][1],[2][2] The major cause of Bell palsy is believed to be an

Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides

Abstract: The concept of site-specific integration of fragments into macrocyclic entities has not yet found application in the realm of synthetic chemistry. Here we show that the reduced amidicity of aziridine amide bonds provides an entry point for the site-specific integration of amino acids and peptide fragments into the homodetic cyclic peptide architecture. This new synthetic operation improves both the convergence and divergence of cyclic peptide synthesis.

PEGylation and Dimerization of Expressed Proteins under Near Equimolar Conditions with Potassium 2-Pyridyl Acyltrifluoroborates

Abstract: The covalent conjugation of large, functionalized molecules remains a frontier in synthetic chemistry, as it requires rapid, chemoselective reactions. The potassium acyltrifluoroborate (KAT)–hydroxylamine amide-forming ligation shows promise for conjugations of biomolecules under aqueous, acidic conditions, but the variants reported to date are not suited to ligations at micromolar concentrations. We now report that 2-pyridyl KATs display significantly enhanced ligation kinetics over their aryl counterparts. Following their facile, one-step incorporation onto the termini of polyethylene glycol (PEG) chains, we show that 2-pyridyl KATs can be applied to the construction of protein–polymer conjugates in excellent (>95%) yield. Four distinct expressed, folded proteins equipped with a hydroxylamine could be PEGylated with 2–20 kDa 2-pyridyl mPEG KATs in high yield and with near-equimolar amounts of coupling partners. Furthermore, the use of a bis 2-pyridyl PEG KAT enables the covalent homodimerization of prot...

Small Heterocycles in Multicomponent Reactions

Abstract: Benjamin H. Rotstein,†,‡ Serge Zaretsky,† Vishal Rai,†,§ and Andrei K. Yudin*,† †Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario Canada, M5S 3H6 ‡Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, United States Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, Indore By-pass Road, Bhauri, Bhopal 462 066, MP India

Nonribosomal Peptide Synthesis-Principles and Prospects.

Abstract: Nonribosomal peptide synthetases (NRPSs) are large multienzyme machineries that assemble numerous peptides with large structural and functional diversity. These peptides include more than 20 marketed drugs, such as antibacterials (penicillin, vancomycin), antitumor compounds (bleomycin), and immunosuppressants (cyclosporine). Over the past few decades biochemical and structural biology studies have gained mechanistic insights into the highly complex assembly line of nonribosomal peptides. This Review provides state-of-the-art knowledge on the underlying mechanisms of NRPSs and the variety of their products along with detailed analysis of the challenges for future reprogrammed biosynthesis. Such a reprogramming of NRPSs would immediately spur chances to generate analogues of existing drugs or new compound libraries of otherwise nearly inaccessible compound structures.

Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes

Abstract: Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices

Peptide stapling techniques based on different macrocyclisation chemistries

Abstract: Peptide stapling is a strategy for constraining short peptides typically in an alpha-helical conformation. Stapling is carried out by covalently linking the side-chains of two amino acids, thereby forming a peptide macrocycle. There is an expanding repertoire of stapling techniques based on different macrocyclisation chemistries. In this tutorial review, we categorise and analyse key examples of peptide stapling in terms of their synthesis and applicability to biological systems.