Peptoid macrocycles: making the rounds with peptidomimetic oligomers.

Macrocyclic constraints are often employed to rigidify the conformation of flexible oligomeric systems. This approach has recently been used to organize the structure of peptoid oligomers, which are peptidomimetics composed of chemically diverse N-substituted glycine monomer units. In this review, we describe advances in the synthesis and characterization of cyclic peptoids. We evaluate how the installation of covalent constraints between the oligomer termini or side chains has been effective in defining peptoid conformations. We also discuss the potential applications for this promising family of macrocyclic peptidomimetics.

[1]  Jieping Zhu,et al.  Conformation-directed macrocyclization reactions , 2005 .

[2]  M. Finn,et al.  Head-to-tail peptide cyclodimerization by copper-catalyzed azide-alkyne cycloaddition. , 2005, Angewandte Chemie.

[3]  Stephen B. H. Kent,et al.  Efficient method for the preparation of peptoids [oligo(N-substituted glycines)] by submonomer solid-phase synthesis , 1992 .

[4]  R. Lokey,et al.  Click chemistry as a macrocyclization tool in the solid-phase synthesis of small cyclic peptides. , 2007, Organic letters.

[5]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[6]  K A Dill,et al.  NMR determination of the major solution conformation of a peptoid pentamer with chiral side chains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  L. Brunsveld,et al.  Stable Helicalβ3-Peptides in Water via Covalent Bridging of Side Chains , 2006 .

[8]  D. Craik,et al.  The cystine knot motif in toxins and implications for drug design. , 2001, Toxicon : official journal of the International Society on Toxinology.

[9]  F. Sansone,et al.  Calixarene-based multivalent ligands. , 2007, Chemical Society reviews.

[10]  Nucleation and stability of hydrogen-bond surrogate-based α-helices , 2006 .

[11]  L. Brunsveld,et al.  Stable helical peptoids via covalent side chain to side chain cyclization. , 2008, Organic & biomolecular chemistry.

[12]  M. Arnaout,et al.  Coming to grips with integrin binding to ligands. , 2002, Current opinion in cell biology.

[13]  U. Pieper,et al.  Carbanion or amide? First charge density study of parent 2-picolyllithium. , 2009, Angewandte Chemie.

[14]  A. Napolitano,et al.  Synthesis, structures, and properties of nine-, twelve-, and eighteen-membered N-benzyloxyethyl cyclic alpha-peptoids. , 2008, Chemical communications.

[15]  C. K. Andrade,et al.  Design and synthesis of cyclic RGD pentapeptoids by consecutive Ugi reactions. , 2008, Organic letters.

[16]  J. Dale,et al.  Cyclic oligopeptides of sarcosine (N-methylglycine) , 1969 .

[17]  U. Pieper,et al.  Carbanion oder Amid? Elektronendichteuntersuchung am 2-Picolyllithium-Stammsystem† , 2009 .

[18]  Ivan Huc,et al.  Aromatic Oligoamide Foldamers , 2004 .

[19]  P. Wipf.  Synthetic Studies of Biologically Active Marine Cyclopeptides , 1995 .

[20]  S. Fournel,et al.  Small multivalent architectures mimicking homotrimers of the TNF superfamily member CD40L: delineating the relationship between structure and effector function. , 2007, Journal of the American Chemical Society.

[21]  M. Goodman,et al.  Triple helical stabilities of guest-host collagen mimetic structures. , 1999, Bioorganic & medicinal chemistry.

[22]  A. P. Davis,et al.  A Synthetic Lectin Analog for Biomimetic Disaccharide Recognition , 2007, Science.

[23]  Helen E Blackwell,et al.  Structure-function relationships in peptoids: recent advances toward deciphering the structural requirements for biological function. , 2009, Organic & biomolecular chemistry.

[24]  H. Kricheldorf,et al.  Cyclic polypeptides by thermal polymerization of α‐amino acid N‐carboxyanhydrides , 2008 .

[25]  D. Spellmeyer,et al.  Nmr Structural Characterization of Oligo-N-Substituted Glycine Lead Compounds from a Combinatorial Library , 2004, Molecular Diversity.

[26]  Vladimir Frecer,et al.  QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1. , 2006, Bioorganic & medicinal chemistry.

[27]  K. Dill,et al.  Structural and spectroscopic studies of peptoid oligomers with alpha-chiral aliphatic side chains. , 2003, Journal of the American Chemical Society.

[28]  R. Raines,et al.  Macrocyclic scaffold for the collagen triple helix. , 2006, Organic letters.

[29]  H. Blackwell,et al.  Design and synthesis of macrocyclic peptomers as mimics of a quorum sensing signal from Staphylococcus aureus. , 2008, Organic letters.

[30]  J. Nowick,et al.  Macrocyclic β-Sheet Peptides that Mimic Protein Quaternary Structure through Intermolecular β-Sheet Interactions , 2007 .

[31]  M. Ghadiri,et al.  Artificial transmembrane ion channels from self-assembling peptide nanotubes , 1994, Nature.

[32]  K. Kirshenbaum,et al.  Peptide cyclization and cyclodimerization by Cu(I)-mediated azide-alkyne cycloaddition. , 2009, The Journal of organic chemistry.

[33]  K. Kirshenbaum,et al.  Clickity-click: highly functionalized peptoid oligomers generated by sequential conjugation reactions on solid-phase support. , 2006, Organic & biomolecular chemistry.

[34]  K. Kirshenbaum,et al.  Peptoid architectures: elaboration, actuation, and application. , 2008, Current opinion in chemical biology.

[35]  Juan R. Granja,et al.  Antibacterial agents based on the cyclic d,l-α-peptide architecture , 2001, Nature.

[36]  John A. Robinson,et al.  Properties and structure-activity studies of cyclic beta-hairpin peptidomimetics based on the cationic antimicrobial peptide protegrin I. , 2005, Bioorganic & medicinal chemistry.

[37]  D. Boturyn,et al.  Multivalent RGD synthetic peptides as potent αVβ3 integrin ligands , 2006 .

[38]  K. Kirshenbaum,et al.  Fit to be tied: conformation-directed macrocyclization of peptoid foldamers. , 2007, Organic letters.

[39]  Juan R. Granja,et al.  Self-Assembling Peptide Nanotubes , 1996 .

[40]  Donghui Zhang,et al.  Cyclic poly(alpha-peptoid)s and their block copolymers from N-heterocyclic carbene-mediated ring-opening polymerizations of N-substituted N-carboxylanhydrides. , 2009, Journal of the American Chemical Society.

[41]  M. Meldal,et al.  High Capacity Poly(ethylene glycol) Based Amino Polymers for Peptide and Organic Synthesis , 2004 .

[42]  M. Cacciarini,et al.  A β-Mannoside-Selective Pyrrolic Tripodal Receptor , 2007 .

[43]  F. Winkler,et al.  The non-planar amide group. , 1971, Journal of molecular biology.

[44]  C. Caumes,et al.  Convenient solution-phase synthesis and conformational studies of novel linear and cyclic alpha,beta-alternating peptoids. , 2009, Organic letters.

[45]  J. Davies.  The cyclization of peptides and depsipeptides , 2003, Journal of peptide science : an official publication of the European Peptide Society.

[46]  L. Wessjohann,et al.  Rapid generation of macrocycles with natural-product-like side chains by multiple multicomponent macrocyclizations (MiBs). , 2008, Organic & biomolecular chemistry.

[47]  T. Kodadek,et al.  Transformation of low-affinity lead compounds into high-affinity protein capture agents. , 2004, Chemistry & biology.

[48]  Qiang Sui,et al.  Kinetics and equilibria of cis/trans isomerization of backbone amide bonds in peptoids. , 2007, Journal of the American Chemical Society.

[49]  Douglas A. Horton,et al.  Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides. , 2003, Organic letters.

[50]  D. Wyss,et al.  Template-Assembled Synthetic Proteins with 4-Helix-Bundle Topology - Total Chemical Synthesis and Conformational Studies , 1992 .

[51]  H. Kolb,et al.  The growing impact of click chemistry on drug discovery. , 2003, Drug discovery today.

[52]  W. Lim,et al.  Improving SH3 domain ligand selectivity using a non-natural scaffold. , 2000, Chemistry & biology.

[53]  Jessica L. Childs-Disney,et al.  Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy. , 2009, Journal of the American Chemical Society.

[54]  M. Wauben,et al.  Major histocompatibility complex class II binding characteristics of peptoid-peptide hybrids. , 2002, Bioorganic & medicinal chemistry.

[55]  K. Burgess.  Solid-phase syntheses of beta-turn analogues to mimic or disrupt protein-protein interactions. , 2001, Accounts of chemical research.

[56]  D. Seebach,et al.  Cyclo‐β‐peptides: Structure and tubular stacking of cyclic tetramers of 3‐aminobutanoic acid as determined from powder diffraction data , 1997 .

[57]  T. Hirata,et al.  A novel polypseudorotaxane composed of cyclic β-peptide as bead component , 2007 .

[58]  K. Sharpless,et al.  Click-Chemie: diverse chemische Funktionalität mit einer Handvoll guter Reaktionen , 2001 .

[59]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[60]  Scott J. Shandler,et al.  Foldamers as versatile frameworks for the design and evolution of function. , 2007, Nature chemical biology.

[61]  R. Lewis,et al.  The interaction of the antimicrobial peptide gramicidin S with lipid bilayer model and biological membranes. , 1999, Biochimica et biophysica acta.

[62]  D. Seebach,et al.  How we drifted into peptide chemistry and where we have arrived at , 2004 .

[63]  M. Ghadiri,et al.  Organische Nanoröhren durch Selbstorganisation , 2001 .

[64]  David J Craik,et al.  Circular proteins--no end in sight. , 2002, Trends in biochemical sciences.

[65]  Horst Kessler,et al.  N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists , 1999 .

[66]  E. Bradley.  A Method for Sequential NMR Assignment of1H and13C Resonances of N-Substituted Glycine Peptoids , 1996 .

[67]  J. Thornton,et al.  Influence of proline residues on protein conformation. , 1991, Journal of molecular biology.

[68]  Richard Bonneau,et al.  A preliminary survey of the peptoid folding landscape. , 2009, Journal of the American Chemical Society.

[69]  K. Kirshenbaum,et al.  Click to fit: versatile polyvalent display on a peptidomimetic scaffold. , 2005, Organic letters.

[70]  N. Abbott,et al.  Nanofibers and lyotropic liquid crystals from a class of self-assembling beta-peptides. , 2008, Angewandte Chemie.

[71]  Samuel H. Gellman,et al.  Foldamers: A Manifesto , 1998 .

[72]  R. Bernini,et al.  New convenient synthesis of iridol. An approach to the synthesis of ubiquinones , 2005 .

[73]  K. Burgess,et al.  Peptidomimetics via copper-catalyzed azide-alkyne cycloadditions. , 2007, Chemical Society reviews.

[74]  S. Korsmeyer,et al.  Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix , 2004, Science.

[75]  Matthew J. Mio,et al.  A field guide to foldamers. , 2001, Chemical reviews.

[76]  Efficient route to C2 symmetric heterocyclic backbone modified cyclic peptides. , 2005, Organic letters.

[77]  M. Jiménez,et al.  Context-Dependence of the Contribution of Disulfide Bonds to β-Hairpin Stability , 2008 .

[78]  S. Benkovic,et al.  Structural requirements for the biosynthesis of backbone cyclic peptide libraries. , 2001, Chemistry & biology.

[79]  Juan R. Granja,et al.  Self-Assembling Organic Nanotubes. , 2001, Angewandte Chemie.

[80]  L. Wessjohann,et al.  Multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs) based on Staudinger and Passerini three-component reactions. , 2008, The Journal of organic chemistry.

[81]  Hartmut Oschkinat,et al.  Design of N-substituted Peptomer Ligands for EVH1 Domains* , 2003, Journal of Biological Chemistry.

[82]  Mary MacDonald and Jeffrey Aube.  Approaches to Cyclic Peptide beeta Turn Mimics , 2001 .

[83]  C. Didierjean,et al.  Cyclic beta-peptoids. , 2008, Organic letters.

[84]  G. Verdine,et al.  An All-Hydrocarbon Cross-Linking System for Enhancing the Helicity and Metabolic Stability of Peptides , 2000 .

[85]  Douglas A. Horton,et al.  Exploring privileged structures: The combinatorial synthesis of cyclic peptides , 2004, Molecular Diversity.

[86]  P. Coric,et al.  On-resin cyclization of peptide ligands of the Vascular Endothelial Growth Factor Receptor 1 by copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition. , 2007, Bioorganic & medicinal chemistry letters.

[87]  M. Ghadiri,et al.  Self-Assembling Cyclic β3-Peptide Nanotubes as Artificial Transmembrane Ion Channels , 1998 .

[88]  Richard W Roberts,et al.  Design of cyclic peptides that bind protein surfaces with antibody-like affinity. , 2007, ACS chemical biology.

[89]  S. Goodman,et al.  Structural and Functional Aspects of RGD-Containing Cyclic Pentapeptides as Highly Potent and Selective Integrin αVβ3 Antagonists , 1996 .

[90]  L. Wessjohann,et al.  Synthesis of steroid-biaryl ether hybrid macrocycles with high skeletal and side chain variability by multiple multicomponent macrocyclization including bifunctional building blocks. , 2006, The Journal of organic chemistry.

[91]  K. Kirshenbaum,et al.  Peptoids on Steroids: Precise Multivalent Estradiol–Peptidomimetic Conjugates Generated via Azide–Alkyne [3+2] Cycloaddition Reactions , 2007 .

[92]  R. Grubbs,et al.  Ring-closing metathesis of olefinic peptides: design, synthesis, and structural characterization of macrocyclic helical peptides. , 2001, The Journal of organic chemistry.

[93]  S. Kimura,et al.  Columnar assembly formation and metal binding of cyclic tri-beta-peptides having terpyridine ligands. , 2007, Organic letters.