Stapled peptide

A cartoon depiction of a stapled peptide. The red coloring depicts a helix, and the green coloring denotes the hydrocarbon staple. Rendering based on PDB 4MZK​.[1]

A stapled peptide is a modified peptide (class A peptidomimetic), typically in an alpha-helical conformation,[2] that is constrained by a synthetic brace ("staple").[3] The staple is formed by a covalent linkage between two amino acid side-chains, forming a peptide macrocycle. Staples, generally speaking, refer to a covalent linkage of two previously independent entities. Peptides with multiple, tandem staples are sometimes referred to as stitched peptides.[4][5] Among other applications, peptide stapling is notably used to enhance the pharmacologic performance of peptides.[5]

  1. ^ Douse, CH; Maas, SJ; Thomas, JC; Garnett, JA; Sun, Y; Cota, E; Tate, EW (17 October 2014). "Crystal structures of stapled and hydrogen bond surrogate peptides targeting a fully buried protein-helix interaction". ACS Chemical Biology. 9 (10): 2204–9. doi:10.1021/cb500271c. PMID 25084543.
  2. ^ Lau, Yu Heng; Andrade, Peterson de; Wu, Yuteng; Spring, David R. (2014-12-08). "Peptide stapling techniques based on different macrocyclisation chemistries". Chemical Society Reviews. 44 (1): 91–102. doi:10.1039/C4CS00246F. ISSN 1460-4744. PMID 25199043.
  3. ^ Kim, Young-Woo; Grossmann, Tom N.; Verdine, Gregory L. (2011). "Synthesis of all-hydrocarbon stapled α-helical peptides by ring-closing olefin metathesis". Nature Protocols. 6 (6): 761–771. doi:10.1038/nprot.2011.324. ISSN 1750-2799. PMID 21637196. S2CID 45832954.
  4. ^ Hilinski, Gerard J.; Kim, Young-Woo; Hong, Jooyeon; Kutchukian, Peter S.; Crenshaw, Charisse M.; Berkovitch, Shaunna S.; Chang, Andrew; Ham, Sihyun; Verdine, Gregory L. (2014-09-03). "Stitched α-Helical Peptides via Bis Ring-Closing Metathesis". Journal of the American Chemical Society. 136 (35): 12314–12322. doi:10.1021/ja505141j. ISSN 0002-7863. PMID 25105213.
  5. ^ a b Verdine, GL; Hilinski, GJ (2012). "Stapled Peptides for Intracellular Drug Targets". Protein Engineering for Therapeutics, Part B. Methods in Enzymology. Vol. 503. pp. 3–33. doi:10.1016/B978-0-12-396962-0.00001-X. ISBN 9780123969620. PMID 22230563.