Recent Advance in Chemical and Enzymatic Approaches in Peptide Macrocyclization
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Amide Bond Formation and Peptide Coupling
Tetrahedron 61 (2005) 10827–10852 Tetrahedron report number 740 Amide bond formation and peptide coupling Christian A. G. N. Montalbetti* and Virginie Falque Evotec, 112 Milton Park, Abingdon OX14 4SD, UK Received 2 August 2005 Available online 19 September 2005 Contents 1. Introduction ................................................................. 10828 2. Amide bond formation: methods and strategies ....................................... 10828 2.1. Acyl halides . .......................................................... 10829 2.1.1. Acyl chlorides .................................................... 10829 2.1.1.1. Acyl chloride formation ...................................... 10829 2.1.1.2. Coupling reactions with acyl chlorides ........................... 10831 2.1.1.3. Limitations of acyl chlorides .................................. 10831 2.1.2. Acyl fluorides .................................................... 10831 2.1.3. Acyl bromides .................................................... 10832 2.2. Acyl azides . .......................................................... 10832 2.3. Acylimidazoles using CDI ................................................. 10833 2.4. Anhydrides . .......................................................... 10834 2.4.1. Symmetric anhydrides .............................................. 10834 2.4.2. Mixed anhydrides .................................................. 10834 2.4.2.1. Mixed carboxylic anhydrides .................................. 10834 2.4.2.2. Mixed carbonic anhydrides ................................... -
Amide-Forming Chemical Ligation Via O-Acyl Hydroxamic Acids
Amide-forming chemical ligation via O-acyl hydroxamic acids Daniel L. Dunkelmanna,1, Yuki Hirataa,1, Kyle A. Totaroa, Daniel T. Cohena, Chi Zhanga, Zachary P. Gatesa,2, and Bradley L. Pentelutea,2 aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved February 28, 2018 (received for review October 20, 2017) The facile rearrangement of “S-acyl isopeptides” to native peptide ligation have relied on the use of thiol nucleophiles to form bonds via S,N-acyl shift is central to the success of native chemical S-acyl isopeptides, which undergo rapid S,N-acyl shifts through ligation, the widely used approach for protein total synthesis. small rings. An exception is the use of selenocysteine (23–26) α Proximity-driven amide bond formation via acyl transfer reactions and peptide- selenoesters (27, 28), which exhibit analogous but in other contexts has proven generally less effective. Here, we heightened reactivity. show that under neutral aqueous conditions, “O-acyl isopeptides” We sought to expand the scope of nucleophiles that might be derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; employed in acyl transfer-based chemical ligation, and to rein- Asp(β-HA)] rearrange to form native peptide bonds via an O,N-acyl vestigate the possibility of O,N-acyl transfer across medium-size shift. This process constitutes a rare example of an O,N-acyl shift rings. Hydroxamic acids (29) were found to be sufficiently re- that proceeds rapidly across a medium-size ring (t1/2 ∼ 15 min), active to enable the formation of an O-acyl isopeptide from a α and takes place in water with minimal interference from hydroly- peptide- thioester and an N-terminal Asp(β-HA)-peptide at sis. -
Protein Ligation: an Enabling Technology for the Biophysical Analysis of Proteins Vasant Muralidharan & Tom W Muir
REVIEW Protein ligation: an enabling technology for the biophysical analysis of proteins methods Vasant Muralidharan & Tom W Muir Biophysical techniques such as fluorescence spectroscopy and nuclear magnetic .com/nature e resonance (NMR) spectroscopy provide a window into the inner workings of proteins. These approaches make use of probes that can either be naturally present within the .natur w protein or introduced through a labeling procedure. In general, the more control one has over the type, location and number of probes in a protein, then the more information one can extract from a given biophysical analysis. Recently, two related approaches have http://ww emerged that allow proteins to be labeled with a broad range of physical probes. Expressed oup r protein ligation (EPL) and protein trans-splicing (PTS) are both intein-based approaches G that permit the assembly of a protein from smaller synthetic and/or recombinant pieces. Here we provide some guidelines for the use of EPL and PTS, and highlight how the lishing b dovetailing of these new protein chemistry methods with standard biophysical techniques Pu has improved our ability to interrogate protein function, structure and folding. Nature 6 An intimate understanding of protein structure and studying protein structure and function in vitro. The goal 200 function remains a principal goal of molecular biology. of this review is to provide an overview of these protein- © The seemingly byzantine structure-activity relationships engineering approaches, with a particular eye toward the underlying protein function make this endeavor extreme- nonspecialist interested in using these techniques to gener- ly challenging and one that requires ever more sophistica- ate labeled proteins for biophysical studies. -
Rapid Flow-Based Peptide Synthesis
Rapid Flow-Based Peptide Synthesis The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Simon, Mark D., Patrick L. Heider, Andrea Adamo, Alexander A. Vinogradov, Surin K. Mong, Xiyuan Li, Tatiana Berger, et al. “Rapid Flow-Based Peptide Synthesis.” ChemBioChem 15, no. 5 (March 11, 2014): 713–720. As Published http://dx.doi.org/10.1002/cbic.201300796 Publisher Wiley Blackwell Version Author's final manuscript Citable link http://hdl.handle.net/1721.1/96181 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ NIH Public Access Author Manuscript Chembiochem. Author manuscript; available in PMC 2015 March 21. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Chembiochem. 2014 March 21; 15(5): 713–720. doi:10.1002/cbic.201300796. Rapid Flow-Based Peptide Synthesis Mark D. Simona, Patrick L. Heiderb, Andrea Adamob, Alexander A. Vinogradova, Surin K. Monga, Xiyuan Lia, Tatiana Bergera, Rocco L. Policarpoa, Chi Zhanga, Yekui Zoua, Xiaoli Liaoa, Alexander M. Spokoynya, Prof Klavs F. Jensenb, and Prof Bradley L. Pentelutea Bradley L. Pentelute: [email protected] aDepartment of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States bDepartment of Chemical Engeneering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States Abstract A flow-based solid phase peptide synthesis methodology that enables the incorporation of an amino acid residue every 1.8 minutes under automatic control, or every three minutes under manual control, is described. -
Synthesis of Peptide and Protein Thioesters Through an N→S Acyl Shift
Native Chemical Thioesterification: Synthesis of Peptide and Protein Thioesters through an N→S Acyl Shift Jaskiranjit Kang A thesis submitted in partial fulfilment of the requirements for the degree award of: Doctor of Philosophy University College London Department of Chemistry 2010 Native Chemical Thioesterification: Synthesis of Peptide and Protein Thioesters through an N→S Acyl Shift Declaration I, Jaskiranjit Kang, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Native Chemical Thioesterification: Synthesis of Peptide and Protein Thioesters through an N→S Acyl Shift Abstract The total chemical synthesis of a protein provides atomic-level control over its covalent structure, however polypeptides prepared by solid phase peptide synthesis are limited to approximately fifty amino acid residues. This limitation has been overcome by 'Native Chemical Ligation‘, which involves amide bond formation between two unprotected polypeptides: a peptide with a C-terminal thioester and an N-terminal cysteinyl peptide. Synthesis of the required peptide thioester is difficult, particularly by Fmoc-chemistry. During our studies towards the semisynthesis of erythropoietin, we discovered reaction conditions that reversed Native Chemical Ligation and generated peptide and protein thioesters through an N→S acyl transfer. O HS H3N O O O + H3O RSH N S SR H O A peptide with both a Gly-Cys and an Ala-Cys-Pro-glycolate ester sequence was selectively thioesterified between the Gly-Cys sequence upon microwave-heating at 80 °C with 30 % v/v 3-mercaptopropionic acid (MPA), to afford the peptide-Gly-MPA thioester (84 % yield). -
An Explorative Study Towards the Chemical Synthesis of the Immunoglobulin G1 Fc CH3 Domain
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Paris Lodron University of Salzburg Received: 10 June 2018 Revised: 26 August 2018 Accepted: 6 September 2018 DOI: 10.1002/psc.3126 RESEARCH ARTICLE An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain Luigi Grassi1,2 | Cornelia Roschger2 | Vesna Stanojlović2 | Chiara Cabrele1,2 1 Christian Doppler Laboratory for Innovative Tools for Biosimilar Characterization, Monoclonal antibodies, fusion proteins including the immunoglobulin fragment c (Ig Fc) University of Salzburg, Hellbrunner Strasse 34, CH2‐CH3 domains, and engineered antibodies are prominent representatives of an 5020 Salzburg, Austria 2 Department of Biosciences, University of important class of drugs and drug candidates, which are referred to as biotherapeutics Salzburg, Billrothstrasse 11, 5020 Salzburg, or biopharmaceuticals. These recombinant proteins are highly heterogeneous due to Austria their glycosylation pattern. In addition, enzyme‐independent reactions, like Correspondence Chiara Cabrele, Department of Biosciences, deamidation, dehydration, and oxidation of sensitive side chains, may contribute to University of Salzburg, Billrothstrasse 11, their heterogeneity in a minor amount. To investigate the biological impact of a spon- 5020 Salzburg, Austria. Email: [email protected] taneous chemical modification, especially if found to be recurrent in a biotherapeutic, Funding information it would be necessary to reproduce it in a homogeneous manner. Herein, we undertook Austrian Federal Ministry of Science, an explorative study towards the chemical synthesis of the IgG1 Fc CH3 domain, which Research, and Economy; Land Salzburg; Start‐ up Grant of the State of Salzburg; University has been shown to undergo spontaneous changes like succinimide formation and of Salzburg methionine oxidation. -
The Investigation of Peptide and Protein-Glycosaminoglycan Binding
The Investigation of Peptide and Protein-Glycosaminoglycan Binding Interactions using Fluorescent Probes By Anthony F. Rullo A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Department of Chemistry University of Toronto Copyright by Anthony F. Rullo 2012 Abstract The Investigation of Peptide and Protein-Glycosaminoglycan Binding Interactions using Fluorescent Probes Doctor of Philosophy Graduate Department of Chemistry University of Toronto Anthony F. Rullo 2012 The structural complexity of glycosaminoglycans (GAGs) such as heparin and heparan sulfate (HS) and their numerous biological roles, brings forth the need to develop new methods, capable of studying GAGs and their interactions with peptides and proteins under native settings. This thesis explores the development of chemical tools to study heparin/HS binding interactions under physiologically relevant conditions using fluorescence. In chapter 2, we designed peptide-based quinolinium probes to study the structural requirements of cationic peptides required for high affinity peptide-heparin interactions. These fluorescent probes enabled the study of peptide- heparin interactions at nM concentrations allowing the calculation of peptide-heparin binding constants. It was observed that peptides with positive charge displayed on one face of an α-helix in a continuous arrangement bound to heparin with the highest affinity and that heparin likely prefers to bind to these peptides while remaining in an extended conformation. In chapter 3, we set out to study an important biological role of HS which involves the binding and sequestering of proteins at the cell surface, facilitating endocytosis. HS has been implicated ii in the mechanism of cell penetrating peptide (CPP) cell uptake, with different CPPs showing different degrees of HS dependence on uptake as well as different mechanisms of entry. -
Application of the Logic of Cysteine-Free Native Chemical Ligation to the Synthesis of Human Parathyroid Hormone (Hpth)
Application of the logic of cysteine-free native chemical ligation to the synthesis of Human Parathyroid Hormone (hPTH) Shiying Shanga, Zhongping Tana, and Samuel J. Danishefskya,b,1 aBio-Organic Chemistry Laboratory, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065; and bDepartment of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027 Contributed by Samuel J. Danishefsky, February 24, 2011 (sent for review December 13, 2010) The power of chemical synthesis of large cysteine-free polypep- stable forms of hPTH, where “pharmacolability” is attenuated tides has been significantly enhanced through the use of nonpro- without undercutting biological activity, would be of great inter- teogenic constructs which bear strategically placed thiol groups, est (26). It is also of interest to interrogate the consequences enabling native chemical ligation. Central to these much expanded of employing nonproteogenic inserts (27). While this goal can capabilities is the specific, radical-induced, metal-free dethiolation, be accomplished by cleverly designed recombinant methods, che- which can be accomplished in aqueous medium. mical synthesis could well be more convenient for servicing the initial production of probe structures for such structure-activity alanine ligation ∣ desulfurization ∣ leucine ligation ∣ peptide ∣ relationship (SAR) evaluations (28, 29). Previously, the chemical valine ligation synthesis of hPTH required either the solid phase synthesis of an 84-mer-long peptide or the assembly of fully protected peptide he chemical synthesis of proteins offers the potential of segments. Such methods are not ideal for the generation of ana- Tsolving a multitude of problems in biomedical sciences (1). logs (30–33). -
Synthesis of Native Proteins by Chemical Ligation∗
P1: FDC/FGE P2: FDC July 12, 2000 11:26 AR102 CHAP29 Annu. Rev. Biochem. 2000. 69:923–60 Copyright c 2000 by Annual Reviews. All rights reserved SYNTHESIS OF NATIVE PROTEINS BY CHEMICAL LIGATION∗ Philip E. Dawson1 and Stephen B. H. Kent2 1The Scripps Research Institute, La Jolla, California 92037; e-mail: [email protected]; 2Gryphon Sciences, South San Francisco, California 94080; e-mail: skent@gryphonsci. com Key Words chemical protein synthesis, thioester, protein, peptide, solid phase synthesis, polymer-supported synthesis, protein engineering ■ Abstract In just a few short years, the chemical ligation of unprotected peptide segments in aqueous solution has established itself as the most practical method for the total synthesis of native proteins. A wide range of proteins has been prepared. These synthetic molecules have led to the elucidation of gene function, to the discovery of novel biology, and to the determination of new three-dimensional protein structures by both NMR and X-ray crystallography. The facile access to novel analogs provided by chemical protein synthesis has led to original insights into the molecular basis of protein function in a number of systems. Chemical protein synthesis has also enabled the systematic development of proteins with enhanced potency and specificity as candidate therapeutic agents. CONTENTS INTRODUCTION: Protein Science in the Postgenome Era ...................924 DOMAINS: Building Blocks of the Protein World .........................925 CHEMICAL PROTEIN SYNTHESIS: The State of the Art in 1990 .............926 SYNTHETIC-PEPTIDE CHEMISTRY: Useful but Bounded .................926 CHEMICAL LIGATION OF UNPROTECTED PEPTIDE SEGMENTS .........929 NATIVE CHEMICAL LIGATION .................................... 933 BIOCHEMICAL PEPTIDE LIGATION ................................ 935 Protein Splicing ................................................ 935 Conformationally Assisted Ligation ................................. -
Hybrid-Phase Native Chemical Ligation Approaches to Overcome the Limitations of Protein Total Synthesis
Hybrid-Phase Native Chemical Ligation Approaches to Overcome the Limitations of Protein Total Synthesis DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ruixuan Ryan Yu Graduate Program in the Ohio State Biochemistry Program The Ohio State University 2016 Committee: Jennifer J. Ottesen – Advisor Michael G. Poirier Michael A. Freitas Dennis Bong Copyrighted by Ruixuan Ryan Yu 2016 Abstract Total protein synthesis allows the preparation of proteins with chemically diverse modifications. The numerous advantages of total synthesis are sometimes offset by some major limitations. Protein synthesis is a non-trivial task involving many chemical steps, and these steps increase with the size of the protein. Therefore, larger proteins are difficult to synthesize with high yield. We have developed a strategy which we term hybrid-phase native chemical ligation (NCL) to overcome some of the limitations of size and yield. Hybrid-phase NCL combines ligating peptides on a solid support (solid-phase NCL) and in solution (solution-phase NCL) to maximize synthetic yield. We have successfully used this method to synthesize triple-acetylated histone H4-K5ac,K12ac,K91ac and, for the first time, acetylated centromeric histone CENP-A-K124ac (CpA-K124ac). In order to improve the yield of CENP-A total synthesis, we have incorporated a convergent ligation element in our hybrid-phase strategy. This new approach reduced the number of purification steps, leading to a synthetic yield that was almost triple that of the original approach. Finally, we introduce the convergent solid-phase hybrid NCL approach that allows the preparation of a long peptide segment bearing a masked thioester on a solid support. -
United States Patent (19) (11) 4,436,912 Wheeler 45) Mar
United States Patent (19) (11) 4,436,912 Wheeler 45) Mar. 13, 1984 54) 7-(2-(2-AMINOOXAZOL-4-YL)-2-(OX (56) References Cited MINO)ACETAMIDO CEPHALOSPORIN ANTBOTCS AND INTERMEDIATES U.S. PATENT DOCUMENTS THEREFOR 4,152,432 5/1979 Iteymes et al. ...................... 424/246 (75) Inventor: William J. Wheeler, Indianapolis, 4,258,041 3/1981 O'Callaghan et al............... 424/246 Ind. Primary Examiner-Donald G. Daus Assignee: Eli Lilly and Company, Indianapolis, Assistant Examiner-G. Hendricks (73) Attorney, Agent, or Firm-Paul C. Steinhardt; Arthur R. Ind. Whale; William B. Scanlon (21) Appl. No.: 417,242 57 ABSTRACT Filed: Sep. 13, 1982 22) Cephalosporin broad spectrum antibiotics possessing a Related U.S. Application Data 7A-2-(2-aminooxazol)-4-yl)-2-(substituted OX iminolacetamido side chain and a variety of substituents (62) Division of Ser. No. 300,140, Sep. 8, 1981. at the 3-position of the cephalosporins are claimed. Also (51) Int. Cl............................................. CO7D 263/30 claimed are intermediates in the synthesis of the above (52) U.S. Cl. .................................... 548/233; 548/236; cephalosporin antibiotics. 548/257; 548/473; 544/25; 544/21; 424/246. (58) Field of Search ........................ 548/233,236, 257 25 Claims, No Drawings 4,436,912 1. 2 7-2-(2-AMINOOXAZOL-4-yl)-2-(OX MINOACETAMDO CEPHALOSPORIN O A ANTIBOTCS AND INTERMEDIATES O HN THEREFOR 5 2 t S This application is a division of application Ser. No. 300,140 filed Sept. 8, 1981. YN i?- N BACKGROUND OF THE INVENTION O N / R3 This invention relates to cephalosporin antibiotic OR compounds and intermediates in the synthesis thereof. -
Coupling Additives 3
Issue in Honor of Drs. Cynthia A. and Bruce E. Maryanoff ARKIVOC 2010 (viii) 189-250 Evolution of amide bond formation Madeleine M. Joullié and Kenneth M. Lassen Department of Chemistry , University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, U. S. A. E-mail: [email protected] This paper is dedicated to Drs Bruce E. Maryanoff and Cynthia A. Maryanoff for their outstanding contribution to organic chemistry as industrial chemists Abstract The presence of carboxamide groups is found in a large array of biologically important compounds. Peptides and proteins play an important role in modern biology. A key step in peptide production is the formation of the peptide bond, which involves amide bond formation. Chemical synthesis of large peptides by intermolecular coupling of smaller peptides using conventional peptide bond-forming techniques did not realize its potential advantages until recently. Using an approach based on highly specific and efficient chemical ligation of two peptide segments, the two subunits were ligated to form a new peptide bond. Native chemical ligation extended the concept by creating a native peptide bond and providing new approaches to protein engineering. Keywords: Amide bond formation, coupling reagent, peptide, chemical ligation, native chemical ligation Table of Contents Introduction 1. Amide Bond Formation 1.1. Approaches to amide bond formation 1.2. Racemization 2. Coupling Additives 3. Common Coupling Reagents 3.1. Azides 3.2. Active esters 3.3. Acyl halides 3.4. Anhydrides ISSN 1551-7012 Page 189 ©ARKAT USA, Inc. Issue in Honor of Drs. Cynthia A. and Bruce E. Maryanoff ARKIVOC 2010 (viii) 189-250 3.5.