Abstract
Protein–protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Linear peptide drugs, however, can be applied therapeutically as protein recognition motifs only to a limited extent because of their poor permeability, decreased receptor selectivity, and proteolytic stability. A major strategy in peptide chemistry is directed toward chemical modification and macrocyclization in order to limit a peptide’s conformational possibilities, to increase its chemical and enzymatic stability, to prolong the time of action, and to increase activity and selectivity toward the receptor.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Jin L, Wang W, Fang G (2014) Targeting protein–protein interaction by small molecules. Annu Rev Pharmacol Toxicol 54:435–456
Wright PE, Dyson HJ (2015) Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol 16:18–29
Mammen M, Shakhnovich EI, Whitesides GM (1998) Using a convenient, quantitative model for torsional entropy to establish qualitative trends for molecular processes that restrict conformational freedom. J Org Chem 63:3168–3175
Zorzi A, Deyle K, Heinis C (2017) Cyclic peptide therapeutics: past, present and future. Curr Opin Chem Biol 38:24–29
White CJ, Yudin AK (2011) Contemporary strategies for peptide macrocyclization. Nat Chem 3:509–524
Marshall GR, Bosshard HE (1972) Angiotensin II. Studies on the biologically active conformation. Circ Res 31:143–150
Garcia-Echeverria C, Chene P, Blommers MJ, Furet P (2000) Discovery of potent antagonists of the interaction between human double minute 2 and tumor suppressor p53. J Med Chem 43:3205–3208
Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright RD, Wagner G, Verdine GL, Korsmeyer SJ (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305(5689):1466–1470
Calvo JC, Choconta KC, Diaz D, Orozco O, Bravo MM, Espejo F, Salazar LM, Guzman F, Patarroyo ME (2003) An alpha helix conformationally restricted peptide is recognized by cervical carcinoma patients’ sera. J Med Chem 46:5389–5394
Kemp DS, Boyd JG, Muendel CC (1991) The helical s constant for alanine in water derived from template-nucleated helices. Nature 352:451–454
Chang YS, Graves B, Guerlavais V, Tovar C, Packman K, To KH, Olson KA, Kesavan K, Gangurde P, Mukherjee A, Baker T, Darlak K, Elkin C, Filipovic Z, Qureshi FZ, Cai H, Berry P, Feyfant E, Shi XE, Horstick J, Annis DA, Manning AM, Fotouhi N, Nash H, Vassilev LT, Sawyer TK (2013) Stapled alpha-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy. Proc Natl Acad Sci U S A 110:E3445–E3454
Madala PK, Tyndall JD, Nall T, Fairlie DP (2010) Update 1 of: proteases universally recognize beta strands in their active sites. Chem Rev 110:PR1–P31
Loughlin WA, Tyndall JD, Glenn MP, Hill TA, Fairlie DP (2010) Update 1 of: beta-strand mimetics. Chem Rev 110:PR32–PR69
McCauley JA, McIntyre CJ, Rudd MT, Nguyen KT, Romano JJ, Butcher JW, Gilbert KF, Bush KJ, Holloway MK, Swestock J, Wan BL, Carroll SS, DiMuzio JM, Graham DJ, Ludmerer SW, Mao SS, Stahlhut MW, Fandozzi CM, Trainor N, Olsen DB, Vacca JP, Liverton NJ (2010) Discovery of vaniprevir (MK-7009), a macrocyclic hepatitis C virus NS3/4a protease inhibitor. J Med Chem 53:2443–2463
Jiang Y, Andrews SW, Condroski KR, Buckman B, Serebryany V, Wenglowsky S, Kennedy AL, Madduru MR, Wang B, Lyon M, Doherty GA, Woodard BT, Lemieux C, Geck Do M, Zhang H, Ballard J, Vigers G, Brandhuber BJ, Stengel P, Josey JA, Beigelman L, Blatt L, Seiwert SD (2014) Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease. J Med Chem 57:1753–1769
Ruiz-Gomez G, Tyndall JD, Pfeiffer B, Abbenante G, Fairlie DP (2010) Update 1 of: over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure. Chem Rev 110:PR1–P41
Che Y, Marshall GR (2008) Privileged scaffolds targeting reverse-turn and helix recognition. Expert Opin Ther Targets 12:101–114
Chalmers DK, Marshall GR (1995) Pro-D-NMe-amino acid and D-Pro-NMe-amino acid: simple, efficient reverse-turn constraints. J Am Chem Soc 117:5927–5937
Chung YJ, Huck BR, Christianson LA, Stanger HE, Krauthäuser S, Powell DR, Gellman SH (2000) Stereochemical control of hairpin formation in β-peptides containing dinipecotic acid reverse turn segments. J Am Chem Soc 122:3995–4004
Finch AM, Wong AK, Paczkowski NJ, Wadi SK, Craik DJ, Fairlie DP, Taylor SM (1999) Low-molecular-weight peptidic and cyclic antagonists of the receptor for the complement factor C5a. J Med Chem 42:1965–1974
Liu H, Kim HR, Deepak R, Wang L, Chung KY, Fan H, Wei Z, Zhang C (2018) Orthosteric and allosteric action of the C5a receptor antagonists. Nat Struct Mol Biol 25:472–481
Acknowledgments
I am grateful to Prof. Garland R. Marshall for his mentorship at Washington University on peptide chemistry and to many Pfizer colleagues, e.g., Thomas Maggie, Peter Jones, Matthew Hayward, and Adam Gilbert, for their insights and fruitful discussions on the design of cyclic peptides for human diseases.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Che, Y. (2019). Design of Cyclic Peptides as Protein Recognition Motifs. In: Goetz, G. (eds) Cyclic Peptide Design. Methods in Molecular Biology, vol 2001. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9504-2_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9504-2_6
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-9503-5
Online ISBN: 978-1-4939-9504-2
eBook Packages: Springer Protocols