Discovery and optimization of peptide macrocycles

References

• Giordanetto F, Kihlberg J. Macrocyclic drugs and clinical candidates: what can medicinal chemists learn from their properties? J Med Chem. 2014;57:278–295. DOI:10.1021/jm400887j
   PubMed Web of Science ®Google Scholar
• Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44:235–249. DOI:10.1016/S1056-8719(00)00107-6
   PubMed Web of Science ®Google Scholar
• Veber DF, Johnson SR, Cheng HY, et al. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45:2615–2623. DOI:10.1021/jm020017n
   PubMed Web of Science ®Google Scholar
• Craik DJ, Fairlie DP, Liras S, et al. The future of peptide‐based drugs. Chem Biol Drug Des. 2013;81:136–147. DOI:10.1111/cbdd.12055
   PubMed Web of Science ®Google Scholar
• Northfield SE, Wang CK, Schroeder CI, et al. Disulfide-rich macrocyclic peptides as templates in drug design. Euro J Med Chem. 2014;77:248–257. DOI:10.1016/j.ejmech.2014.03.011
   PubMed Web of Science ®Google Scholar
• Sawyer TK, Guerlavais V, Darlak K, et al. Macrocyclic α-helical peptide drug discovery. In: Levin J, editor. Macrocycles in drug discovery. London: RSC Drug Discovery Series; 2015. p. 339–366.
   Google Scholar
• Montalban-Lopez M, Sanchez-Hidalgo M, Cebrian R, et al. Discovering the bacterial circular proteins: bacteriocins, cyanobactins, and pilins. J Biol Chem. 2012;287:27007–27013. DOI:10.1074/jbc.R112.354688
   PubMed Web of Science ®Google Scholar
• Göransson U, Burman R, Gunasekera S, et al. Circular proteins from plants and fungi. J Biol Chem. 2012;287:27001–27006. DOI:10.1074/jbc.R111.300129
   PubMed Web of Science ®Google Scholar
• Lehrer RI, Cole AM, Selsted ME. θ-Defensins: cyclic peptides with endless potential. J Biol Chem. 2012;287:27014–27019. DOI:10.1074/jbc.R112.346098
   PubMed Web of Science ®Google Scholar
• Luo H, Hong SY, Sgambelluri RM, et al. Peptide macrocyclization catalyzed by a prolyl oligopeptidase involved in alpha-amanitin biosynthesis. Chem Biol. 2014;21:1610–1617. DOI:10.1016/j.chembiol.2014.10.015
   PubMedGoogle Scholar
• Gruber CW, Elliott AG, Ireland DC, et al. Distribution and evolution of circular miniproteins in flowering plants. Plant Cell. 2008;20:2471–2483. DOI:10.1105/tpc.108.062331
   PubMed Web of Science ®Google Scholar
• Sletten K, Gran L. Some molecular properties of kalatapeptide B-1. A uterotonic polypeptide isolated from Oldenlandia affinis DC. Medd Nor Farm Selsk. 1973;7:69–82.
   Google Scholar
• Craik DJ, Daly NL, Bond T, et al. Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J Mol Biol. 1999;294:1327–1336. DOI:10.1006/jmbi.1999.3383
   PubMed Web of Science ®Google Scholar
• Wang CKL, Quentin K, Chiche L, et al. CyBase: A database of cyclic protein sequences and structures, with application in protein discovery and engineering. Nucleic Acids Res. 2008;36:D206–210. DOI:10.1093/nar/gkm953
   PubMed Web of Science ®Google Scholar
• Colgrave ML, Craik DJ. Thermal, chemical, and enzymatic stability of the cyclotide Kalata B1: the importance of the cyclic cystine knot. Biochemistry. 2004;43:5965–5975. DOI:10.1021/bi049711q
   PubMed Web of Science ®Google Scholar
• Daly NL, Gustafson KR, Craik DJ. The role of the cyclic peptide backbone in the anti-HIV activity of the cyclotide kalata B1. FEBS Lett. 2004;574:69–72. DOI:10.1016/j.febslet.2004.08.007
   PubMed Web of Science ®Google Scholar
• Felizmenio-Quimio ME, Daly NL, Craik DJ. Circular proteins in plants: solution structure of a novel macrocyclic trypsin inhibitor from Momordica cochinchinensis. J Biol Chem. 2001;276:22875–22882. DOI:10.1074/jbc.M101666200
   PubMed Web of Science ®Google Scholar
• Chiche L, Heitz A, Gelly JC, et al. Squash inhibitors: from structural motifs to macrocyclic knottins. Curr Protein Pept Sci. 2004;5:341–349. DOI:10.2174/1389203043379477
   PubMed Web of Science ®Google Scholar
• Gustafson KR, Walton LK, Sowder RC Jr., et al. New circulin macrocyclic polypeptides from Chassalia parvifolia. J Nat Prod. 2000;63:176–178. DOI:10.1021/np990432r
   PubMed Web of Science ®Google Scholar
• Tam JP, Lu YA, Yang JL, et al. An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides. Proc Natl Acad Sci USA. 1999;96:8913–8918. DOI:10.1073/pnas.96.16.8913
   PubMed Web of Science ®Google Scholar
• Ireland DC, Colgrave ML, Craik DJ. A novel suite of cyclotides from Viola odorata: Sequence variation and the implications for structure, function and stability. Biochem J. 2006;400:1–12. DOI:10.1042/bj20060627
   PubMed Web of Science ®Google Scholar
• Plan MR, Göransson U, Clark RJ, et al. The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides. ChemBioChem. 2007;8:1001–1011. DOI:10.1002/cbic.200700097
   PubMed Web of Science ®Google Scholar
• Simonsen SM, Sando L, Rosengren KJ, et al. Alanine scanning mutagenesis of the prototypic cyclotide reveals a cluster of residues essential for bioactivity. J Biol Chem. 2008;283:9805–9813. DOI:10.1074/jbc.M709303200
   PubMed Web of Science ®Google Scholar
• Lindholm P, Göransson U, Johansson S, et al. Cyclotides: A novel type of cytotoxic agents. Mol Cancer Ther. 2002;1:365–369.
   PubMed Web of Science ®Google Scholar
• Gerlach SL, Rathinakumar R, Chakravarty G, et al. Anticancer and chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers. 2010;94:617–625. DOI:10.1002/bip.21435
   PubMed Web of Science ®Google Scholar
• Jennings C, West J, Waine C, et al. Biosynthesis and insecticidal properties of plant cyclotides: the cyclic knotted proteins from Oldenlandia affinis. Proc Natl Acad Sci USA. 2001;98:10614–10619. DOI:10.1073/pnas.191366898
   PubMed Web of Science ®Google Scholar
• Colgrave ML, Kotze AC, Ireland DC, et al. The anthelmintic activity of the cyclotides: natural variants with enhanced activity. ChemBioChem. 2008;9:1939–1945. DOI:10.1002/cbic.200800174
   PubMed Web of Science ®Google Scholar
• Plan MR, Saska I, Cagauan AG, et al. Backbone cyclised peptides from plants show molluscicidal activity against the rice pest Pomacea canaliculata (golden apple snail). J Agric Food Chem. 2008;56:5237–5241. DOI:10.1021/jf800302f
   PubMed Web of Science ®Google Scholar
• Barbeta BL, Marshall AT, Gillon AD, et al. Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae. Proc Natl Acad Sci USA. 2008;105:1221–1225. DOI:10.1073/pnas.0710338104
   PubMed Web of Science ®Google Scholar
• Daly NL, Clark RJ, Craik DJ. Disulfide folding pathways of cystine knot proteins. Tying the knot within the circular backbone of the cyclotides. J Biol Chem. 2003;278:6314–6322. DOI:10.1074/jbc.M210492200
   PubMed Web of Science ®Google Scholar
• Göransson U, Craik DJ. Disulfide mapping of the cyclotide kalata B1. Chemical proof of the cystic cystine knot motif. J Biol Chem. 2003;278:48188–48196. DOI:10.1074/jbc.M308771200
   PubMed Web of Science ®Google Scholar
• Cheneval O, Schroeder CI, Durek T, et al. Fmoc-based synthesis of disulfide-rich cyclic peptides. J Org Chem. 2014;79:5538–5544. DOI:10.1021/jo500699m
   PubMed Web of Science ®Google Scholar
• Clark RJ, Daly NL, Craik DJ. Structural plasticity of the cyclic-cystine-knot framework: implications for biological activity and drug design. Biochem J. 2006;394:85–93. DOI:10.1042/BJ20051691
   PubMed Web of Science ®Google Scholar
• Ji Y, Majumder S, Millard M, et al. In vivo activation of the p53 tumor suppressor pathway by an engineered cyclotide. J Am Chem Soc. 2013;135:11623–11633. DOI:10.1021/ja405108p
   PubMed Web of Science ®Google Scholar
• D’Souza C, Henriques ST, Wang CK, et al. Using the MCoTI-II cyclotide scaffold to design a stable cyclic peptide antagonist of SET, a protein overexpressed in human cancer. Biochemistry. 2016;55:396–405. DOI:10.1021/acs.biochem.5b00529
   PubMed Web of Science ®Google Scholar
• Wang CK, Gruber CW, Cemazar M, et al. Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis. ACS Chem Biol. 2014;9:156–163. DOI:10.1021/cb400548s
   PubMed Web of Science ®Google Scholar
• Wong CTT, Rowlands DK, Wong CH, et al. Orally active peptidic bradykinin B1 receptor antagonists engineered from a cyclotide scaffold for inflammatory pain treatment. Angew Chem Int Ed. 2012;51:5620–5624. DOI:10.1002/anie.201200984
   PubMed Web of Science ®Google Scholar
• Huang YH, Henriques ST, Wang CK, et al. Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide scaffold. Sci Rep. 2015;5:12974. DOI:10.1038/srep12974
   PubMed Web of Science ®Google Scholar
• Aboye T, Meeks CJ, Majumder S, et al. Design of a MCoTI-based cyclotide with angiotensin (1-7)-like activity. Molecules. 2016;21. DOI:10.3390/molecules21020152
   PubMed Web of Science ®Google Scholar
• Eliasen R, Daly NL, Wulff BS, et al. Design, synthesis, structural and functional characterization of novel melanocortin agonists based on the cyclotide kalata B1. J Biol Chem. 2012;287:40493–40501. DOI:10.1074/jbc.M112.395442
   PubMed Web of Science ®Google Scholar
• Chan LY, Gunasekera S, Henriques ST, et al. Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. Blood. 2011;118:6709–6717. DOI:10.1182/blood-2011-06-359141
   PubMed Web of Science ®Google Scholar
• Thell K, Hellinger R, Sahin E, et al. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis. Proc Natl Acad Sci USA. 2016;113:3960–3965. DOI:10.1073/pnas.1519960113
   PubMed Web of Science ®Google Scholar
• Greenwood KP, Daly NL, Brown DL, et al. The cyclic cystine knot miniprotein MCoTI-II is internalized into cells by macropinocytosis. Int J Biochem Cell Biol. 2007;39:2252–2264. DOI:10.1016/j.biocel.2007.06.016
   PubMed Web of Science ®Google Scholar
• Cascales L, Henriques ST, Kerr MC, et al. Identification and characterization of a new family of cell-penetrating peptides: cyclic cell-penetrating peptides. J Biol Chem. 2011;286:36932–36943. DOI:10.1074/jbc.M111.264424
   PubMed Web of Science ®Google Scholar
• Contreras J, Elnagar AYO, Hamm-Alvarez SF, et al. Cellular uptake of cyclotide MCoTI-I follows multiple endocytic pathways. J Control Release. 2011;155:134–143. DOI:10.1016/j.jconrel.2011.08.030
   PubMed Web of Science ®Google Scholar
• Henriques ST, Huang YH, Chaousis S, et al. The prototypic cyclotide Kalata B1 has a unique mechanism of entering cells. Chem Biol. 2015;22:1087–2097. DOI:10.1016/j.chembiol.2015.07.012
   PubMedGoogle Scholar
• D’Souza C, Henriques ST, Wang CK, et al. Structural parameters modulating the cellular uptake of disulfide-rich cyclic cell-penetrating peptides: MCoTI-II and SFTI-1. Euro J Med Chem. 2014;88:10–18. DOI:10.1016/j.ejmech.2014.06.047
   PubMed Web of Science ®Google Scholar
• Nguyen GKT, Wang S, Qiu Y, et al. Butelase 1 is an Asx-specific ligase enabling peptide macrocyclization and synthesis. Nat Chem Biol. 2014;10:732–738. DOI:10.1038/nchembio.1586
   PubMed Web of Science ®Google Scholar
• Harris KS, Durek T, Kaas Q, et al. Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase. Nat Commun. 2015;6. DOI:10.1038/ncomms10199
   Web of Science ®Google Scholar
• Tang YQ, Yuan J, Osapay G, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science. 1999;286:498–502. DOI:10.1126/science.286.5439.498
   PubMed Web of Science ®Google Scholar
• Conibear AC, Rosengren KJ, Harvey PJ, et al. Structural characterization of the cyclic cystine ladder motif of θ-defensins. Biochemistry. 2012;51:9718–97126. DOI:10.1021/bi301363a
   PubMed Web of Science ®Google Scholar
• Conibear AC, Rosengren KJ, Daly NL, et al. The cyclic cystine ladder in theta-defensins is important for structure and stability, but not antibacterial activity. J Biol Chem. 2013;288:10830–10840. DOI:10.1074/jbc.M113.451047
   PubMed Web of Science ®Google Scholar
• Conibear AC, Craik DJ. The chemistry and biology of theta defensins. Angew Chem Int Ed Engl. 2014;53:10612–10623. DOI:10.1002/anie.201402167
   PubMed Web of Science ®Google Scholar
• Tongaonkar P, Tran P, Roberts K, et al. Rhesus macaque theta-defensin isoforms: expression, antimicrobial activities, and demonstration of a prominent role in neutrophil granule microbicidal activities. J Leukoc Biol. 2011;89:283–290. DOI:10.1189/jlb.0910535
   PubMed Web of Science ®Google Scholar
• Schaal JB, Tran D, Tran P, et al. Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis. PLoS One. 2012;7:e51337. DOI:10.1371/journal.pone.0051337
   PubMed Web of Science ®Google Scholar
• Wilmes M, Stockem M, Bierbaum G, et al. Killing of staphylococci by θ-defensins involves membrane impairment and activation of autolytic enzymes. Antibiotics. 2014;3:617–631. DOI:10.3390/antibiotics3040617
   Google Scholar
• Tongaonkar P, Trinh KK, Schaal JB, et al. Rhesus macaque theta-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-kappaB and MAPK pathways. J Leukoc Biol. 2015;98:1061–1070. DOI:10.1189/jlb.3A0315-102R
   PubMed Web of Science ®Google Scholar
• Wohlford-Lenane CL, Meyerholz DK, Perlman S, et al. Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J Virol. 2009;83:11385–11390. DOI:10.1128/jvi.01363-09
   PubMed Web of Science ®Google Scholar
• Oh YT, Tran D, Buchanan TA, et al. theta-Defensin RTD-1 improves insulin action and normalizes plasma glucose and FFA levels in diet-induced obese rats. Am J Physiol Endocrinol Metab. 2015;309:e154–160. DOI:10.1152/ajpendo.00131.2015
   Google Scholar
• Cole AM, Hong T, Boo LM, et al. Retrocyclin: A primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci USA. 2002;99:1813–1818. DOI:10.1073/pnas.052706399
   PubMed Web of Science ®Google Scholar
• Yang C, Boone L, Nguyen TX, et al. Theta-defensin pseudogenes in HIV-1-exposed, persistently seronegative female sex-workers from Thailand. Infect Genet Evol. 2005;5:11–15. DOI:10.1016/j.meegid.2004.05.006
   PubMedGoogle Scholar
• Conibear AC, Bochen A, Rosengren KJ, et al. The cyclic cystine ladder of theta-defensins as a stable, bifunctional scaffold: a proof-of-concept study using the integrin-binding RGD motif. ChemBioChem. 2014;15:451–459. DOI:10.1002/cbic.201300568
   PubMed Web of Science ®Google Scholar
• Aboye TL, Ha H, Majumder S, et al. Design of a novel cyclotide-based CXCR4 antagonist with anti-Human Immunodeficiency Virus (HIV)-1 activity. J Med Chem. 2012;55:10729–10734. DOI:10.1021/jm301468k
   PubMed Web of Science ®Google Scholar
• Conibear AC, Chaousis S, Durek T, et al. Approaches to the stabilization of bioactive epitopes by grafting and peptide cyclization. Biopolymers. 2016;106:89–100. DOI:10.1002/bip.22767
   PubMed Web of Science ®Google Scholar
• Luckett S, Garcia RS, Barker JJ, et al. High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seeds. J Mol Biol. 1999;290:525–533. DOI:10.1006/jmbi.1999.2891
   PubMed Web of Science ®Google Scholar
• Elliott AG, Delay C, Liu H, et al. Evolutionary origins of a bioactive peptide buried within preproalbumin. Plant Cell. 2014;26:981–995. DOI:10.1105/tpc.114.123620
   PubMed Web of Science ®Google Scholar
• Qi RF, Song ZW, Chi CW. Structural features and molecular evolution of bowman-birk protease inhibitors and their potential application. Acta Biochim Biophys Sinica. 2005;37:283–292. DOI:10.1111/j.1745-7270.2005.00048.x
   PubMed Web of Science ®Google Scholar
• Korsinczky ML, Clark RJ, Craik DJ. Disulfide bond mutagenesis and the structure and function of the head-to-tail macrocyclic trypsin inhibitor SFTI-1. Biochemistry. 2005;44:1145–1153. DOI:10.1021/bi048297r
   PubMed Web of Science ®Google Scholar
• Craik DJ, Swedberg JE, Mylne JS, et al. Cyclotides as a basis for drug design. Exp Opin Drug Disc. 2012;7:179–194. DOI:10.1517/17460441.2012.661554
   PubMed Web of Science ®Google Scholar
• Chan LY, Craik DJ, Daly NL. Cyclic thrombospondin-1 mimetics: grafting of a thrombospondin sequence into circular disulfide-rich frameworks to inhibit endothelial cell migration. Biosci Rep. 2015;35. DOI:10.1042/bsr20150210
   PubMed Web of Science ®Google Scholar
• Wang CK, Northfield SE, Huang YH, et al. Inhibition of tau aggregation using a naturally-occurring cyclic peptide scaffold. Euro J Med Chem. 2016;109:342–349. DOI:10.1016/j.ejmech.2016.01.006
   PubMed Web of Science ®Google Scholar
• De Veer SJ, Swedberg JE, Akcan M, et al. Engineered protease inhibitors based on sunflower trypsin inhibitor-1 (SFTI-1) provide insights into the role of sequence and conformation in Laskowski mechanism inhibition. Biochem J. 2015;469:243–253. DOI:10.1042/bj20150412
   PubMed Web of Science ®Google Scholar
• Fittler H, Depp A, Avrutina O, et al. Engineering a constrained peptidic scaffold towards potent and selective furin inhibitors. ChemBioChem. 2015;16:2441–2444. DOI:10.1002/cbic.201500447
   PubMed Web of Science ®Google Scholar
• Jendrny C, Beck-Sickinger AG. Inhibition of kallikrein-related peptidases 7 and 5 by grafting serpin reactive-center loop sequences onto sunflower trypsin inhibitor-1 (SFTI-1). ChemBioChem. 2015;17:719–726. DOI:10.1002/cbic.201500539
   PubMed Web of Science ®Google Scholar
• Swedberg JE, Nigon LV, Reid JC, et al. Substrate-guided design of a potent and selective kallikrein-related peptidase inhibitor for kallikrein 4. Chem Biol. 2009;16:633–643. DOI:10.1016/j.chembiol.2009.05.008
   PubMed Web of Science ®Google Scholar
• Okinyo-Owiti DP, Dong Q, Ling B, et al. Evaluating the cytotoxicity of flaxseed orbitides for potential cancer treatment. Toxicol Rep. 2015;2:1014–1018. DOI:10.1016/j.toxrep.2015.06.011
   PubMed Web of Science ®Google Scholar
• Gaymes TJ, Cebrat M, Siemion IZ, et al. Cyclolinopeptide A (CLA) mediates its immunosuppressive activity through cyclophilin-dependent calcineurin inactivation. FEBS Letters. 1997;418:224–227. DOI:10.1016/S0014-5793(97)01345-8
   PubMed Web of Science ®Google Scholar
• Katarzyńska J, Mazur A, Rudzińska E, et al. Cyclolinopeptide derivatives modify methotrexate-induced suppression of the humoral immune response in mice. Euro J Med Chem. 2011;46:4608–4617. DOI:10.1016/j.ejmech.2011.07.040
   PubMed Web of Science ®Google Scholar
• Scott CP, Abel-Santos E, Wall M, et al. Production of cyclic peptides and proteins in vivo. Proc Natl Acad Sci USA. 1999;96:13638–13643. DOI:10.1073/pnas.96.24.13638
   PubMed Web of Science ®Google Scholar
• Smith JM, Frost JR, Fasan R. Emerging strategies to access peptide macrocycles from genetically encoded polypeptides. J Org Chem. 2013;78:3525–3531. DOI:10.1021/jo400119s
   PubMed Web of Science ®Google Scholar
• Passioura T, Katoh T, Goto Y, et al. Selection-based discovery of druglike macrocyclic peptides. Annu Rev Biochem. 2014;83:727–752. DOI:10.1146/annurev-biochem-060713-035456
   PubMed Web of Science ®Google Scholar
• Lennard KR, Tavassoli A. Peptides come round: using SICLOPPS libraries for early stage drug discovery. Chemistry. 2014;20:10608–10614. DOI:10.1002/chem.201403117
   PubMed Web of Science ®Google Scholar
• Clark RJ, Fischer H, Dempster L, et al. Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII. Proc Natl Acad Sci USA. 2005;102:13767–13772. DOI:10.1073/pnas.0504613102
   PubMed Web of Science ®Google Scholar
• Clark RJ, Jensen J, Nevin ST, et al. The engineering of an orally active conotoxin for the treatment of neuropathic pain. Angew Chem Int Ed. 2010;49:6545–6548. DOI:10.1002/anie.201000620
   PubMed Web of Science ®Google Scholar
• Halai R, Callaghan B, Daly NL, et al. Effects of cyclization on stability, structure, and activity of α-conotoxin RgIA at the α9α10 nicotinic acetylcholine receptor and GABAB receptor. J Med Chem. 2011;54:6984–6992. DOI:10.1021/jm201060r
   PubMed Web of Science ®Google Scholar
• Armishaw CJ, Dutton JL, Craik DJ, et al. Establishing regiocontrol of disulfide bond isomers of alpha-conotoxin ImI via the synthesis of N-to-C cyclic analogs. Biopolymers. 2010;94:307–313. DOI:10.1002/bip.21360
   PubMed Web of Science ®Google Scholar
• Armishaw CJ, Jensen AA, Balle LD, et al. Improving the stability of alpha-conotoxin AuIB through N-to-C cyclization: the effect of linker length on stability and activity at nicotinic acetylcholine receptors. Antioxid Redox Signal. 2011;14:65–76. DOI:10.1089/ars.2010.3458
   PubMed Web of Science ®Google Scholar
• Lovelace ES, Gunasekera S, Alvarmo C, et al. Stabilization of alpha-conotoxin AuIB: influences of disulfide connectivity and backbone cyclization. Antioxid Redox Signal. 2011;14:87–95. DOI:10.1089/ars.2009.3068
   PubMed Web of Science ®Google Scholar
• Lovelace ES, Armishaw CJ, Colgrave ML, et al. Cyclic MrIA: A stable and potent cyclic conotoxin with a aovel topological fold that targets the norepinephrine transporter. J Med Chem. 2006;49:6561–6568. DOI:10.1021/jm060299h
   PubMed Web of Science ®Google Scholar
• Hemu X, Taichi M, Qiu Y, et al. Biomimetic synthesis of cyclic peptides using novel thioester surrogates. Biopolymers. 2013;100:492–501. DOI:10.1002/bip.22308
   PubMed Web of Science ®Google Scholar
• Akcan M, Clark RJ, Daly NL, et al. Transforming conotoxins into cyclotides: backbone cyclization of P-superfamily conotoxins. Biopolymers. 2015;104:682–692. DOI:10.1002/bip.22699
   PubMed Web of Science ®Google Scholar
• Chan LY, Zhang VM, Huang YH, et al. Cyclization of the antimicrobial peptide gomesin with native chemical ligation: influences on stability and bioactivity. ChemBioChem. 2013;14:617–624. DOI:10.1002/cbic.201300034
   PubMed Web of Science ®Google Scholar
• Jensen JE, Mobli M, Brust A, et al. Cyclisation increases the stability of the sea anemone peptide APETx2 but decreases its activity at acid-sensing ion channel 3. Marine Drugs. 2012;10:1511–1527. DOI:10.3390/md10071511
   PubMed Web of Science ®Google Scholar
• Clark RJ, Preza GC, Tan CC, et al. Design, synthesis, and characterization of cyclic analogues of the iron regulatory peptide hormone hepcidin. Biopolymers. 2013;100:519–526. DOI:10.1002/bip.22350
   PubMed Web of Science ®Google Scholar
• Scanlon MJ, Naranjo D, Thomas L, et al. Solution structure and proposed binding mechanism of a novel potassium channel toxin κ-conotoxin PVIIA. Structure. 1997;5:1585–1597. DOI:10.1016/S0969-2126(97)00307-9
   PubMed Web of Science ®Google Scholar
• Kwon S, Bosmans F, Kaas Q, et al. Efficient enzymatic cyclization of an inhibitory cystine knot-containing peptide. Biotechnol Bioeng. 2016;113:2202–2212. DOI:10.1002/bit.25993
   PubMed Web of Science ®Google Scholar
• Timmerman P, Beld J, Puijk WC, et al. Rapid and quantitative cyclization of multiple peptide loops onto synthetic scaffolds for structural mimicry of protein surfaces. ChemBioChem. 2005;6:821–824. DOI:10.1002/cbic.200400374
   PubMed Web of Science ®Google Scholar
• Chen S, Morales-Sanfrutos J, Angelini A, et al. Structurally diverse cyclisation linkers impose different backbone conformations in bicyclic peptides. ChemBioChem. 2012;13:1032–1038. DOI:10.1002/cbic.201200049
   PubMed Web of Science ®Google Scholar
• Chen S, Bertoldo D, Angelini A, et al. Peptide ligands stabilized by small molecules. Angew Chem Int Ed Engl. 2014;53:1602–1606. DOI:10.1002/anie.201309459
   PubMed Web of Science ®Google Scholar
• Heinis C, Winter G. Encoded libraries of chemically modified peptides. Curr Opin Chem Biol. 2015;26:89–98. DOI:10.1016/j.cbpa.2015.02.008
   PubMed Web of Science ®Google Scholar
• Heinis C, Rutherford T, Freund S, et al. Phage-encoded combinatorial chemical libraries based on bicyclic peptides. Nat Chem Biol. 2009;5:502–507. DOI:10.1038/nchembio.184
   PubMed Web of Science ®Google Scholar
• Baeriswyl V, Rapley H, Pollaro L, et al. Bicyclic peptides with optimized ring size inhibit human plasma kallikrein and its orthologues while sparing paralogous proteases. ChemMedChem. 2012;7:1173–1176. DOI:10.1002/cmdc.201200071
   PubMed Web of Science ®Google Scholar
• Baeriswyl V, Calzavarini S, Chen S, et al. A synthetic factor XIIa inhibitor blocks selectively intrinsic coagulation initiation. ACS Chem Biol. 2015;10:1861–1870. DOI:10.1021/acschembio.5b00103
   PubMed Web of Science ®Google Scholar
• Bertoldo D, Khan MMG, Dessen P, et al. Phage selection of peptide macrocycles against β-catenin to interfere with Wnt signaling. ChemMedChem. 2016;11:834–839. DOI:10.1002/cmdc.201500557
   PubMed Web of Science ®Google Scholar
• Pollaro L, Raghunathan S, Morales-Sanfrutos J, et al. Bicyclic peptides conjugated to an albumin-binding tag diffuse efficiently into solid tumors. Mol Cancer Ther. 2015;14:151–161. DOI:10.1158/1535-7163.MCT-14-0534
   PubMed Web of Science ®Google Scholar
• Wallbrecher R, Depré L, Verdurmen WPR, et al. Exploration of the design principles of a cell-penetrating bicylic peptide scaffold. Bioconjugate Chem. 2014;25:955–964. DOI:10.1021/bc500107f
   PubMed Web of Science ®Google Scholar
• Schafmeister CE, Po J, Verdine GL. An all-hydrocarbon cross-linking system for enhancing the helicity and metabolic stability of peptides. J Am Chem Soc. 2000;122:5891–5892. DOI:10.1021/ja000563a
   Web of Science ®Google Scholar
• Aileron therapeutics successfully completes first-ever stapled peptide clinical trial. Business Wire. Cambridge, MA: Aileron Therapeutics, 2013; [cited 2016 Jul 12]. Available from: http://www.businesswire.com/news/home/20130507005467/en/Aileron-Therapeutics-Successfully-Completes-First-Ever-Stapled-Peptide
   Google Scholar
• Aileron therapeutics initiates phase 1 cancer study of ALRN-6924 in advanced hematologic and solid malignancies with wild type p53. Business Wire. Cambridge, MA: Aileron Therapeutics; 2015 [cited 2016 Jul 12]. Available from: http://www.businesswire.com/news/home/20150212005199/en/Aileron-Therapeutics-Initiates-Phase-1-Cancer-Study
   Google Scholar
• Okamoto T, Zobel K, Fedorova A, et al. Stabilizing the pro-apoptotic BimBH3 helix (BimSAHB) does not necessarily enhance affinity or biological activity. ACS Chem Biol. 2013;8:297–302. DOI:10.1021/cb3005403
   PubMed Web of Science ®Google Scholar
• Li YC, Rodewald LW, Hoppmann C, et al. A versatile platform to analyze low-affinity and transient protein-protein interactions in living cells in real time. Cell Rep. 2014;9:1946–1958. DOI:10.1016/j.celrep.2014.10.058
   PubMed Web of Science ®Google Scholar
• Cromm PM, Spiegel J, Grossmann TN. Hydrocarbon stapled peptides as modulators of biological function. ACS Chem Biol. 2015;10:1362–1375. DOI:10.1021/cb501020r
   PubMed Web of Science ®Google Scholar
• Chu Q, Moellering RE, Hilinski GJ, et al. Towards understanding cell penetration by stapled peptides. MedChemComm. 2015;6:111–119. DOI:10.1039/C4MD00131A
   Web of Science ®Google Scholar
• Leshchiner ES, Braun CR, Bird GH, et al. Direct activation of full-length proapoptotic BAK. Proc Natl Acad Sci USA. 2013;110:e986–995. DOI:10.1073/pnas.1214313110
   PubMed Web of Science ®Google Scholar
• Bird GH, Gavathiotis E, LaBelle JL, et al. Distinct BimBH3 (BimSAHB) stapled peptides for structural and cellular studies. ACS Chem Biol. 2014;9:831–837. DOI:10.1021/cb4003305
   PubMed Web of Science ®Google Scholar
• Bernal F, Wade M, Godes M, et al. A stapled p53 helix overcomes HDMX-mediated suppression of p53. Cancer Cell. 2010;18:411–422. DOI:10.1016/j.ccr.2010.10.024
   PubMed Web of Science ®Google Scholar
• Brown CJ, Quah ST, Jong J, et al. Stapled peptides with improved potency and specificity that activate p53. ACS Chem Biol. 2013;8:506–512. DOI:10.1021/cb3005148
   PubMed Web of Science ®Google Scholar
• Chang YS, Graves B, Guerlavais V, et al. Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc Natl Acad Sci USA. 2013;110:e3445–3454. DOI:10.1073/pnas.1303002110
   PubMed Web of Science ®Google Scholar
• Long YQ, Huang SX, Zawahir Z, et al. Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors. J Med Chem. 2013;56:5601–5612. DOI:10.1021/jm4006516
   PubMed Web of Science ®Google Scholar
• Phillips C, Roberts LR, Schade M, et al. Design and structure of stapled peptides binding to estrogen receptors. J Am Chem Soc. 2011;133:9696–9699. DOI:10.1021/ja202946k
   PubMed Web of Science ®Google Scholar
• Bird GH, Mazzola E, Opoku-Nsiah K, et al. Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices. Nat Chem Biol. 2016;12:845–852.
   PubMed Web of Science ®Google Scholar
• Pelay-Gimeno M, Glas A, Koch O, et al. Structure-based design of inhibitors of protein–protein interactions: mimicking peptide binding epitopes. Angew Chem Int Ed. 2015;54:8896–8927. DOI:10.1002/anie.201412070
   PubMed Web of Science ®Google Scholar
• Obrecht D, Chevalier E, Moehle K, et al. β-Hairpin protein epitope mimetic technology in drug discovery. Drug Discov Today Technol. 2012;9:e63–69. DOI:10.1016/j.ddtec.2011.07.006
   Google Scholar
• Späth J, Stuart F, Jiang L, et al. Stabilization of a β-hairpin conformation in a cyclic peptide using the templating effect of a heterochiral diproline unit. Helvetica Chimica Acta. 1998;81:1726–1738. DOI:10.1002/(SICI)1522-2675(19980909)81:9<1726::AID-HLCA1726>3.0.CO;2-H
   Web of Science ®Google Scholar
• Schmidt J, Patora-Komisarska K, Moehle K, et al. Structural studies of β-hairpin peptidomimetic antibiotics that target LptD in Pseudomonas sp. Bioorg Med Chem. 2013;21:5806–5810. DOI:10.1016/j.bmc.2013.07.013
   PubMed Web of Science ®Google Scholar
• Srinivas N, Jetter P, Ueberbacher BJ, et al. Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science. 2010;327:1010–1013. DOI:10.1126/science.1182749
   PubMed Web of Science ®Google Scholar
• Vetterli SU, Moehle K, Robinson JA. Synthesis and antimicrobial activity against Pseudomonas aeruginosa of macrocyclic β-hairpin peptidomimetic antibiotics containing N-methylated amino acids. Bioorg Med Chem. 2016. DOI:10.1016/j.bmc.2016.05.027
   PubMed Web of Science ®Google Scholar
• Urfer M, Bogdanovic J, Lo Monte F, et al. A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in escherichia coli. J Biol Chem. 2016;291:1921–1932. DOI:10.1074/jbc.M115.691725
   PubMed Web of Science ®Google Scholar
• Fasan R, Dias RL, Moehle K, et al. Using a beta-hairpin to mimic an alpha-helix: cyclic peptidomimetic inhibitors of the p53-HDM2 protein-protein interaction. Angew Chem Int Ed Engl. 2004;43:2109–2112. DOI:10.1002/anie.200353242
   PubMed Web of Science ®Google Scholar
• Fasan R, Dias RL, Moehle K, et al. Structure-activity studies in a family of beta-hairpin protein epitope mimetic inhibitors of the p53-HDM2 protein-protein interaction. ChemBioChem. 2006;7:515–526. DOI:10.1002/cbic.200500452
   PubMed Web of Science ®Google Scholar
• Hill TA, Lohman R-J, Hoang HN, et al. Cyclic penta- and hexaleucine peptides without N-methylation are orally absorbed. ACS Med Chem Lett. 2014;5:1148–1151. DOI:10.1021/ml5002823
   PubMed Web of Science ®Google Scholar
• Nielsen DS, Hoang HN, Lohman R-J, et al. Improving on nature: making a cyclic heptapeptide orally bioavailable. Angew Chem Int Ed. 2014;53:12059–12063. DOI:10.1002/anie.201405364
   PubMed Web of Science ®Google Scholar
• White TR, Renzelman CM, Rand AC, et al. On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds. Nat Chem Biol. 2011;7:810–817. DOI:10.1038/nchembio.664
   PubMed Web of Science ®Google Scholar
• Beck JG, Chatterjee J, Laufer B, et al. Intestinal permeability of cyclic peptides: common key backbone motifs identified. J Am Chem Soc. 2012;134:12125–12133. DOI:10.1021/ja303200d
   PubMed Web of Science ®Google Scholar
• Marelli UK, Ovadia O, Frank AO, et al. cis-peptide bonds: A key for intestinal permeability of peptides? Chem Euro J. 2015;21:15148–15152. DOI:10.1002/chem.201501600
   PubMed Web of Science ®Google Scholar
• Nielsen DS, Lohman R-J, Hoang HN, et al. Flexibility versus rigidity for orally bioavailable cyclic hexapeptides. ChemBioChem. 2015;16:2289–2293. DOI:10.1002/cbic.201500441
   PubMed Web of Science ®Google Scholar
• Bockus AT, Lexa KW, Pye CR, et al. Probing the physicochemical boundaries of cell permeability and oral bioavailability in lipophilic macrocycles inspired by natural products. J Med Chem. 2015;58:4581–4589. DOI:10.1021/acs.jmedchem.5b00128
   PubMed Web of Science ®Google Scholar
• Bockus AT, Schwochert JA, Pye CR, et al. Going out on a limb: delineating the effects of beta-branching, N-methylation, and side chain size on the passive permeability, solubility, and flexibility of sanguinamide A analogues. J Med Chem. 2015;58:7409–7418. DOI:10.1021/acs.jmedchem.5b00919
   PubMed Web of Science ®Google Scholar