PT-141

A synthetic cyclic heptapeptide characterized in cryo-EM structural studies of class A GPCR–Gs complexes.

View PT-141 in the store

Molecular Profile

Type
Synthetic peptide (cyclic heptapeptide)
Molecular formula
C50H68N14O10
Molecular weight
1,025.18 g/mol
CAS number
189691-06-3
Amino acids
7
Sequence
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
Modification
N-terminal acetylation; norleucine (Nle) substitution; lactam side-chain cyclization (Asp–Lys); D-phenylalanine at position 7; free C-terminal carboxyl (–OH), distinguishing it from the C-terminal amide of Melanotan II.

Mechanism & Target Class

A cyclic heptapeptide sharing the lactam-bridged scaffold of the related peptide Melanotan II. The lactam-bridged cyclic backbone, norleucine substitution, and D-phenylalanine confer conformational constraint and enzymatic stability; the free C-terminal carboxyl distinguishes it structurally from the C-terminal amide of Melanotan II. The relevant binding partners belong to a family of class A G-protein-coupled receptors that couple to Gs and adenylyl cyclase. Cryo-electron microscopy work has resolved one such class A GPCR in complex with peptide agonists and the Gs protein, clarifying the architecture of the receptor pocket engaged by the cyclic peptide backbone (Heyder et al., 2021).

Storage & Handling

Lyophilized
Commonly stored frozen (typically −20°C, −80°C for long-term archival); protected from light and moisture; stable as a lyophilized solid for extended periods under these conditions.
Handling
The cyclic, lactam-bridged backbone confers greater conformational and enzymatic stability than linear α-MSH. Minimize exposure to elevated temperature, light, and repeated freeze–thaw.

Primary Database

PubChem CID 9941379 ↗

References (31)

  1. Reviews

    1

    Li JJ (ed.) (2024). Chemistry and Pharmacology of Drug Discovery (Wiley), ch. 16

    DOI: 10.1002/9781394225156.ch16

  2. 2

    Kingsberg SA, Simon JA. (2021). Expert Opin Pharmacother

    DOI: 10.1080/14656566.2020.1869721

  3. 3

    Mayer D, Lynch SE (2020). Annals of Pharmacotherapy

    DOI: 10.1177/1060028019899152PubMed 31893927

  4. 4

    Dhillon S, Keam SJ (2019). Drugs

    DOI: 10.1007/s40265-019-01187-wPubMed 31429064

  5. 5

    Giuliano F, et al. (2008). J Sex Med

    DOI: 10.1111/j.1743-6109.2007.00690.xPubMed 18086164

  6. 6

    Molinoff PB, et al. (2006). Ann NY Acad Sci

    DOI: 10.1196/annals.1317.063PubMed 16888210

  7. Clinical

    7

    Clayton AH, Kingsberg SA, Portman D, Sadiq A, Krop J, Jordan R, Lucas J, Simon JA (2022). Journal of Women's Health

    PubMed 35230162

  8. 8

    Clayton AH, Kingsberg SA, Portman D, et al. (2022). Journal of Women's Health

    DOI: 10.1089/jwh.2021.0191PubMed 35147466

  9. 9

    Koochaki P, Revicki D, Wilson H, Pokrzywinski R, Jordan R, Lucas J, Williams LA, Sadiq A, Krop J (2021). Journal of Women's Health

    DOI: 10.1089/jwh.2020.8460PubMed 33538638

  10. 10

    Simon JA, et al. (2020). Obstet Gynecol

    DOI: 10.1097/AOG.0000000000003650PubMed 31923053

  11. 11

    Clayton AH, et al. (2020). J Womens Health

    DOI: 10.1089/jwh.2019.8094PubMed 32105569

  12. 12

    Kingsberg SA, et al. (2019). Obstet Gynecol

    DOI: 10.1097/AOG.0000000000003500PubMed 31599839NCT02333071

  13. 13

    Simon JA, Kingsberg SA, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Clayton AH (2019). Obstet Gynecol

    DOI: 10.1097/AOG.0000000000003514PubMed 31599847

  14. 14

    White WB, Myers MG, Jordan R, Lucas J (2017). Journal of Hypertension

    PubMed 27977473

  15. 15

    Clayton AH, Althof SE, Kingsberg S, DeRogatis LR, Kroll R, Goldstein I, Kaminetsky J, Spana C, Lucas J, Jordan R, Portman DJ (2016). Women's Health (London)

    DOI: 10.2217/whe-2016-0018PubMed 27181790NCT01382719

  16. 16

    Clayton AH, et al. (2016). J Sex Med

    DOI: 10.1016/j.jsxm.2016.02.167PubMed 27045261

  17. 17

    Safarinejad MR, Hosseini SY (2008). The Journal of Urology

    PubMed 18206919

  18. 18

    Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R (2006). J Sex Med

    DOI: 10.1111/j.1743-6109.2006.00268.xPubMed 16839319

  19. 19

    Diamond LE, et al. (2006). J Sex Med

    DOI: 10.1111/j.1743-6109.2006.00267.xPubMed 16839320

  20. 20

    Diamond LE, Earle DC, Garcia WD, Spana C (2005). Urology

    PubMed 15833522

  21. 21

    Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB (2004). Int J Impot Res

    DOI: 10.1038/sj.ijir.3901200PubMed 14999221

  22. 22

    Diamond LE, et al. (2004). Int J Impot Res

    DOI: 10.1038/sj.ijir.3901221PubMed 14999224

  23. 23

    Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB (2004). Int J Impot Res

    PubMed 14963471

  24. Primary research

    24

    Suzuki S, Kitanaka C, Okada M (2024). Anticancer Research

    DOI: 10.21873/anticanres.17214PubMed 39197897

  25. 25

    Heyder NA, Kleinau G, Speck D, et al. (2021). Cell Research

    DOI: 10.1038/s41422-021-00569-8PubMed 34561620

  26. 26

    Giuliani D, Mioni C, Bazzani C, et al. (2007). British Journal of Pharmacology

    DOI: 10.1038/sj.bjp.0707115PubMed 17245369

  27. 27

    Shadiack AM, et al. (2004). Pharmacol Biochem Behav

    DOI: 10.1016/j.pbb.2004.04.020PubMed 15251271

  28. 28

    Pfaus JG, Shadiack A, Van Soest T, Tse M, Molinoff P (2004). Proc Natl Acad Sci USA

    DOI: 10.1073/pnas.0400491101PubMed 15226502

  29. 29

    Wessells H, Vanderah TW, Hruby VJ, et al. (2003). Neuroscience

    DOI: 10.1016/S0306-4522(02)00866-7PubMed 12710982

  30. 30

    Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY (2003). Ann NY Acad Sci

    DOI: 10.1111/j.1749-6632.2003.tb03167.xPubMed 12851303

  31. 31

    Guarini S, Bazzani C, Cainazzo MM, Mioni C, Ferrazza G, Vergoni AV, Schiöth HB, Wikberg JES, Bertolini A (1999). J Pharmacol Exp Ther

    DOI: 10.1016/S0022-3565(24)35205-XPubMed 10565821