Macrocycles: lessons from the distant past, recent developments, and future directions

THE GREEN FLUORESCENT PROTEIN

Tsien, R. Y. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.509 · Cited by 6,143

Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability

Hidalgo, I. J., Raub, T. J., & Borchardt, R. T. (1989) · Gastroenterology · doi:10.1016/s0016-5085(89)80072-1 · Cited by 2,396

The Future of Peptide‐based Drugs

Craik, D. J., Fairlie, D. P., Liras, S., & Price, D. (2013) · Chemical Biology & Drug Design · doi:10.1111/cbdd.12055 · Cited by 1,979

Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding

Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., et al. (2009) · Science · doi:10.1126/science.1168750 · Cited by 1,929

Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand

Xiong, J.-P., Stehle, T., Zhang, R., Joachimiak, A., Frech, M., Goodman, S. L., & Arnaout, M. A. (2002) · Science · doi:10.1126/science.1069040 · Cited by 1,613

Mammalian defensins in the antimicrobial immune response

Selsted, M. E., & Ouellette, A. J. (2005) · Nature Immunology · doi:10.1038/ni1206 · Cited by 1,203

The Discovery of Crown Ethers (Noble Lecture)

Pedersen, C. J. (1988) · Angewandte Chemie International Edition in English · doi:10.1002/anie.198810211 · Cited by 1,147

Contemporary strategies for peptide macrocyclization

White, C. J., & Yudin, A. K. (2011) · Nature Chemistry · doi:10.1038/nchem.1062 · Cited by 1,088

An All-Hydrocarbon Cross-Linking System for Enhancing the Helicity and Metabolic Stability of Peptides

Schafmeister, C. E., Po, J., & Verdine, G. L. (2000) · Journal of the American Chemical Society · doi:10.1021/ja000563a · Cited by 1,037

Antibacterial agents based on the cyclic d,l-α-peptide architecture

Fernandez-Lopez, S., Kim, H.-S., Choi, E. C., Delgado, M., Granja, J. R., Khasanov, A., Kraehenbuehl, K., Long, G., Weinberger, D. A., Wilcoxen, K. M., et al. (2001) · Nature · doi:10.1038/35086601 · Cited by 938

Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1

Goldberg, J., Huang, H.-B., Kwon, Y.-G., Greengard, P., Nairn, A. C., & Kuriyan, J. (1995) · Nature · doi:10.1038/376745a0 · Cited by 860

Phage-encoded combinatorial chemical libraries based on bicyclic peptides

Heinis, C., Rutherford, T., Freund, S., & Winter, G. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.184 · Cited by 743

Coexistence of passive and carrier-mediated processes in drug transport

Sugano, K., Kansy, M., Artursson, P., Avdeef, A., Bendels, S., Di, L., Ecker, G. F., Faller, B., Fischer, H., Gerebtzoff, G., et al. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3187 · Cited by 649

DNA-Templated Organic Synthesis and Selection of a Library of Macrocycles

Gartner, Z. J., Tse, B. N., Grubina, R., Doyon, J. B., Snyder, T. M., & Liu, D. R. (2004) · Science · doi:10.1126/science.1102629 · Cited by 503

N‐Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions

Chatterjee, J., Rechenmacher, F., & Kessler, H. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201205674 · Cited by 494

Testing the Conformational Hypothesis of Passive Membrane Permeability Using Synthetic Cyclic Peptide Diastereomers

Rezai, T., Yu, B., Millhauser, G. L., Jacobson, M. P., & Lokey, R. S. (2006) · Journal of the American Chemical Society · doi:10.1021/ja0563455 · Cited by 490

Phage Libraries Displaying Cyclic Peptides with Different Ring Sizes: Ligand Specificities of the RGD-Directed Integrins

Koivunen, E., Wang, B., & Ruoslahti, E. (1995) · Nature Biotechnology · doi:10.1038/nbt0395-265 · Cited by 477

A Perfluoroaryl-Cysteine S N Ar Chemistry Approach to Unprotected Peptide Stapling

Spokoyny, A. M., Zou, Y., Ling, J. J., Yu, H., Lin, Y.-S., & Pentelute, B. L. (2013) · Journal of the American Chemical Society · doi:10.1021/ja400119t · Cited by 474

Stapled Peptides for Intracellular Drug Targets

Verdine, G. L., & Hilinski, G. J. (2012) · Methods in Enzymology · doi:10.1016/b978-0-12-396962-0.00001-x · Cited by 433

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

Stewart, M. L., Fire, E., Keating, A. E., & Walensky, L. D. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.391 · Cited by 418

Conformational Flexibility, Internal Hydrogen Bonding, and Passive Membrane Permeability: Successful in Silico Prediction of the Relative Permeabilities of Cyclic Peptides

Rezai, T., Bock, J. E., Zhou, M. V., Kalyanaraman, C., Lokey, R. S., & Jacobson, M. P. (2006) · Journal of the American Chemical Society · doi:10.1021/ja063076p · Cited by 416

How proteins bind macrocycles

Villar, E. A., Beglov, D., Chennamadhavuni, S., Porco, J. A., Kozakov, D., Vajda, S., & Whitty, A. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1584 · Cited by 400

On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds

White, T. R., Renzelman, C. M., Rand, A. C., Rezai, T., McEwen, C. M., Gelev, V. M., Turner, R. A., Linington, R. G., Leung, S. S. F., Kalgutkar, A. S., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.664 · Cited by 386

The Structure of Proteins

Pauling, L., & Niemann, C. (1939) · Journal of the American Chemical Society · doi:10.1021/ja01876a065 · Cited by 362

Design of peptides, proteins, and peptidomimetics in chi space

Hruby, V. J., Li, G., Haskell-Luevano, C., & Shenderovich, M. (1997) · Biopolymers · doi:10.1002/(sici)1097-0282(1997)43:3<219::aid-bip3>3.0.co;2-y · Cited by 354

Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space

Alex, A., Millan, D. S., Perez, M., Wakenhut, F., & Whitlock, G. A. (2011) · MedChemComm · doi:10.1039/c1md00093d · Cited by 329

β-Hairpin Peptidomimetics: Design, Structures and Biological Activities

Robinson, J. A. (2008) · Accounts of Chemical Research · doi:10.1021/ar700259k · Cited by 321

General approach to the synthesis of short .alpha.-helical peptides

Jackson, D. Y., King, D. S., Chmielewski, J., Singh, S., & Schultz, P. G. (1991) · Journal of the American Chemical Society · doi:10.1021/ja00024a067 · Cited by 313

The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain

Clark, R. J., Jensen, J., Nevin, S. T., Callaghan, B. P., Adams, D. J., & Craik, D. J. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201000620 · Cited by 313

Assessing Helical Protein Interfaces for Inhibitor Design

Bullock, B. N., Jochim, A. L., & Arora, P. S. (2011) · Journal of the American Chemical Society · doi:10.1021/ja206074j · Cited by 300

Rapid and Quantitative Cyclization of Multiple Peptide Loops onto Synthetic Scaffolds for Structural Mimicry of Protein Surfaces

Timmerman, P., Beld, J., Puijk, W. C., & Meloen, R. H. (2005) · ChemBioChem · doi:10.1002/cbic.200400374 · Cited by 295

Biomimetic synthesis and optimization of cyclic peptide antibiotics

Kohli, R. M., Walsh, C. T., & Burkart, M. D. (2002) · Nature · doi:10.1038/nature00907 · Cited by 287

Zwitterionic Ring-Opening Polymerization for the Synthesis of High Molecular Weight Cyclic Polymers

Brown, H. A., & Waymouth, R. M. (2013) · Accounts of Chemical Research · doi:10.1021/ar400072z · Cited by 255

Structural basis for the drug extrusion mechanism by a MATE multidrug transporter

Tanaka, Y., Hipolito, C. J., Maturana, A. D., Ito, K., Kuroda, T., Higuchi, T., Katoh, T., Kato, H. E., Hattori, M., Kumazaki, K., et al. (2013) · Nature · doi:10.1038/nature12014 · Cited by 250

Macrocyclization of Linear Peptides Enabled by Amphoteric Molecules

Hili, R., Rai, V., & Yudin, A. K. (2010) · Journal of the American Chemical Society · doi:10.1021/ja910544p · Cited by 235

Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the α-conotoxin MII

Clark, R. J., Fischer, H., Dempster, L., Daly, N. L., Rosengren, K. J., Nevin, S. T., Meunier, F. A., Adams, D. J., & Craik, D. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504613102 · Cited by 234

Ring-Closing Metathesis of Olefinic Peptides: Design, Synthesis, and Structural Characterization of Macrocyclic Helical Peptides

Blackwell, H. E., Sadowsky, J. D., Howard, R. J., Sampson, J. N., Chao, J. A., Steinmetz, W. E., O'Leary, D. J., & Grubbs, R. H. (2001) · The Journal of Organic Chemistry · doi:10.1021/jo015533k · Cited by 222

What can a chemist learn from nature?s macrocycles? ? A brief, conceptual view

Wessjohann, L. A., Ruijter, E., Garcia-Rivera, D., & Brandt, W. (2005) · Molecular Diversity · doi:10.1007/s11030-005-1314-x · Cited by 222

Site‐Selective Derivatization and Remodeling of Erythromycin A by Using Simple Peptide‐Based Chiral Catalysts

Lewis, C. A., & Miller, S. J. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200601490 · Cited by 216

mRNA display: from basic principles to macrocycle drug discovery

Josephson, K., Ricardo, A., & Szostak, J. W. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2013.10.011 · Cited by 210

Comprehensive analysis of loops at protein-protein interfaces for macrocycle design

Gavenonis, J., Sheneman, B. A., Siegert, T. R., Eshelman, M. R., & Kritzer, J. A. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1580 · Cited by 198

Intestinal Permeability of Cyclic Peptides: Common Key Backbone Motifs Identified

Beck, J. G., Chatterjee, J., Laufer, B., Kiran, M. U., Frank, A. O., Neubauer, S., Ovadia, O., Greenberg, S., Gilon, C., Hoffman, A., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja303200d · Cited by 187

Update 1 of: Proteases Universally Recognize Beta Strands In Their Active Sites

Madala, P. K., Tyndall, J. D. A., Nall, T., & Fairlie, D. P. (2010) · Chemical Reviews · doi:10.1021/cr900368a · Cited by 165

N-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Substituted N-Carboxyanhydrides toward Poly(α-peptoid)s: Kinetic, Mechanism, and Architectural Control

Guo, L., Lahasky, S. H., Ghale, K., & Zhang, D. (2012) · Journal of the American Chemical Society · doi:10.1021/ja210842b · Cited by 161

EPSA: A Novel Supercritical Fluid Chromatography Technique Enabling the Design of Permeable Cyclic Peptides

Goetz, G. H., Philippe, L., & Shapiro, M. J. (2014) · ACS Medicinal Chemistry Letters · doi:10.1021/ml500239m · Cited by 160

Cyclosporin metabolism in transplant patients

Christians, U., & Sewing, K.-F. (1993) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(93)90059-m · Cited by 159

The N-terminal to C-terminal motif in protein folding and function

Mallela, K. M. G., & Englander, S. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409114102 · Cited by 145

Cyclic RGD Peptides Containing β-Turn Mimetics

Haubner, R., Schmitt, W., Hölzemann, G., Goodman, S. L., Jonczyk, A., & Kessler, H. (1996) · Journal of the American Chemical Society · doi:10.1021/ja9608757 · Cited by 135

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

Rand, A. C., Leung, S. S. F., Eng, H. F., Rotter, C. J., Sharma, R., Kalgutkar, A. S. S., Zhang, Y., Varma, M. V. S., Farley, K. A., Khunte, B., et al. (2012) · MedChemComm · doi:10.1039/c2md20203d · Cited by 132

Unusual β-sheet periodicity in small cyclic peptides

Gibbs, A. C., Kondejewski, L. H., Gronwald, W., Nip, A. M., Hodges, R. S., Sykes, B. D., & Wishart, D. S. (1998) · Nature Structural Biology · doi:10.1038/nsb0498-284 · Cited by 115

Strained Cyclophane Macrocycles: Impact of Progressive Ring Size Reduction on Synthesis and Structure

Bogdan, A. R., Jerome, S. V., Houk, K. N., & James, K. (2011) · Journal of the American Chemical Society · doi:10.1021/ja208503y · Cited by 95

Phase Separation As a Strategy Toward Controlling Dilution Effects in Macrocyclic Glaser-Hay Couplings

Bédard, A., & Collins, S. K. (2011) · Journal of the American Chemical Society · doi:10.1021/ja208902t · Cited by 91

Emac – a comparative index for the assessment of macrocyclization efficiency

Collins, J. C., & James, K. (2012) · MedChemComm · doi:10.1039/c2md20176c · Cited by 86

Design, Synthesis, Biological Evaluation, and Structural Characterization of Potent Histone Deacetylase Inhibitors Based on Cyclic α/β-Tetrapeptide Architectures

Montero, A., Beierle, J. M., Olsen, C. A., & Ghadiri, M. R. (2009) · Journal of the American Chemical Society · doi:10.1021/ja809508f · Cited by 83

Synthesis of Difficult Cyclic Peptides by Inclusion of a Novel Photolabile Auxiliary in a Ring Contraction Strategy

Meutermans, W. D. F., Golding, S. W., Bourne, G. T., Miranda, L. P., Dooley, M. J., Alewood, P. F., & Smythe, M. L. (1999) · Journal of the American Chemical Society · doi:10.1021/ja992173y · Cited by 82

Ligand Preorganization May Be Accompanied by Entropic Penalties in Protein–Ligand Interactions

Benfield, A. P., Teresk, M. G., Plake, H. R., DeLorbe, J. E., Millspaugh, L. E., & Martin, S. F. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200600844 · Cited by 81

Conformational constraint in protein ligand design and the inconsistency of binding entropy.

Udugamasooriya, D. G., & Spaller, M. (2008) · Biopolymers · doi:10.1002/bip.20983 · Cited by 76

Keeping dry and crossing membranes

Fernández, A. (2004) · Nature Biotechnology · doi:10.1038/nbt0904-1081 · Cited by 70

Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A

Hu, X., Thomas, D. S., Griffith, R., & Hunter, L. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403071 · Cited by 69

Conformational Analysis of Macrocycles: Finding What Common Search Methods Miss

Bonnet, P., Agrafiotis, D. K., Zhu, F., & Martin, É. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci900238a · Cited by 67

Cyclic Penta- and Hexaleucine Peptides without N -Methylation Are Orally Absorbed

Hill, T. A., Lohman, R., Hoang, H. N., Nielsen, D. S., Scully, C. C. G., Kok, W. M., Liu, L., Lucke, A. J., Stoermer, M. J., Schroeder, C. I., et al. (2014) · ACS Medicinal Chemistry Letters · doi:10.1021/ml5002823 · Cited by 66

Conformationally Homogeneous Cyclic Tetrapeptides: Useful New Three-Dimensional Scaffolds

Glenn, M. P., Kelso, M. J., Tyndall, J. D. A., et al. (2002) · Journal of the American Chemical Society · doi:10.1021/ja029205t · Cited by 61

Exocyclic Control of Turn Induction in Macrocyclic Peptide Scaffolds

Zaretsky, S., Scully, C. C. G., Lough, A. J., & Yudin, A. K. (2013) · Chemistry - A European Journal · doi:10.1002/chem.201303453 · Cited by 59

Spatial Screening for the Identification of the Bioactive Conformation of Integrin Ligands

Weide, T., Modlinger, A., & Kessler, H. (2006) · Springer eBooks · doi:10.1007/128_052 · Cited by 57

Cyclic Modular β-Sheets

Woods, R. J., Brower, J. O., Castellanos, E., Hashemzadeh, M., Khakshoor, O., Russu, W. A., & Nowick, J. S. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0667965 · Cited by 56

Enteral absorption of octreotide: absorption enhancement by polyoxyethylene‐24‐cholesterol ether

Drewe, J., Fricker, G., Vonderscher, J., & Beglinger, C. (1993) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1993.tb12799.x · Cited by 56

Electronic tuning of site-selectivity

Wilcock, B. C., Uno, B. E., Bromann, G. L., Clark, M. J., Anderson, T. M., & Burke, M. D. (2012) · Nature Chemistry · doi:10.1038/nchem.1495 · Cited by 55

Stereoselective Fluorination Alters the Geometry of a Cyclic Peptide: Exploration of Backbone‐Fluorinated Analogues of Unguisin A

Hu, X., Thomas, D. S., Griffith, R., & Hunter, L. (2014) · Angewandte Chemie · doi:10.1002/ange.201403071 · Cited by 54

A New and Useful Method for the Macrocyclization of Linear Peptides

Londregan, A. T., Farley, K. A., Limberakis, C., Mullins, P. B., & Piotrowski, D. W. (2012) · Organic Letters · doi:10.1021/ol301173m · Cited by 53

Cyclative Cleavage through Dipolar Cycloaddition: Polymer‐Bound Azidopeptidylphosphoranes Deliver Locked cis‐ Triazolylcyclopeptides as Privileged Protein Binders

Ahsanullah, A., & Rademann, J. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.200904980 · Cited by 51

Site-Specific Integration of Amino Acid Fragments into Cyclic Peptides

White, C. J., Hickey, J. L., Scully, C. C. G., & Yudin, A. K. (2014) · Journal of the American Chemical Society · doi:10.1021/ja412256f · Cited by 51

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains

Daidone, I., Neuweiler, H., Doose, S., Sauer, M., & Smith, J. C. (2010) · PLoS Comput. Biol. · doi:10.1371/journal.pcbi.1000645 · Cited by 48

Novel macrocyclic HCV NS3 protease inhibitors derived from α-amino cyclic boronates

Li, X., Zhang, Y.-K., Liu, Y., Ding, C. Z., Zhou, Y., Li, Q., Plattner, J. J., Baker, S. J., Zhang, S., Kazmierski, W. M., et al. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.08.022 · Cited by 36

Efficient parallel synthesis of macrocyclic peptidomimetics

Marsault, É., Hoveyda, H. R., Gagnon, R., Peterson, M. L., Vézina, M., Saint‐Louis, C. J., Landry, A., Pinault, J.-F., Ouellet, L., Beauchemin, S., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.06.085 · Cited by 35

Macrocyclization of Organo‐Peptide Hybrids through a Dual Bio‐orthogonal Ligation: Insights from Structure–Reactivity Studies

Frost, J. R., Vitali, F., Jacob, N. T., Brown, M. D., & Fasan, R. (2012) · ChemBioChem · doi:10.1002/cbic.201200579 · Cited by 34

The remarkable sensitivity to acid‐catalyzed peptolysis of peptide chains (endopeptolysis) having a succession of three N‐alkylated amino acid residues

Anteunis, M. J. O., & Auwera, C. V. D. (1988) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1988.tb00038.x · Cited by 33

Conformationally Constrained Cyclic Peptides: Powerful Scaffolds for Asymmetric Catalysis

Zheng, L., Marcozzi, A., Gerasimov, J. Y., & Herrmann, A. P. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201403829 · Cited by 32

Natural macrocyclic molecules have a possible limited structural diversity

Frank, A. T., Farina, N. S., Sawwan, N., et al. (2007) · Molecular Diversity · doi:10.1007/s11030-007-9065-5 · Cited by 32

A Cyclic β-Strand Tripeptide with an α-Helix Like CD Spectrum

Driver, R. W., Hoang, H. N., Abbenante, G., et al. (2009) · Organic Letters · doi:10.1021/ol901181b · Cited by 20

Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production

Isidro-Llobet, A., Kenworthy, M. N., Mukherjee, S., Kopach, M. E., Wegner, K., Gallou, F., Smith, A. G., & Roschangar, F. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.8b03001 · Cited by 473

New Modalities for Challenging Targets in Drug Discovery

Valeur, E., Guéret, S. M., Adihou, H., Gopalakrishnan, R., Lemurell, M., Waldmann, H., Grossmann, T. N., & Plowright, A. T. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611914 · Cited by 382

Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials

Aguirre, T. A. S., Teijeiro-Osorio, D., Rosa, M., Coulter, I. S., Alonso, M. J., & Brayden, D. J. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.02.004 · Cited by 299

RNA Display Methods for the Discovery of Bioactive Macrocycles

Huang, Y., Wiedmann, M. M., & Suga, H. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00430 · Cited by 298

Going Out on a Limb: Delineating The Effects of β-Branching, N -Methylation, and Side Chain Size on the Passive Permeability, Solubility, and Flexibility of Sanguinamide A Analogues

Bockus, A. T., Schwochert, J. A., Pye, C. R., Townsend, C. E., Sok, V., Bednarek, M. A., & Lokey, R. S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00919 · Cited by 135