Peptidomimetics in Cancer Targeting

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2022 Dec 8

PMID 36476230

Authors

Mohammad Mahmoudi Gomari

Shadi Abkhiz

Taha Ghantab Pour

Ehsan Lotfi

Neda Rostami

Fatemeh Nafe Monfared

Babak Ghobari

Mona Mosavi

Behruz Alipour

Nikolay V Dokholyan

Affiliations

Soon will be listed here.

Abstract

The low efficiency of treatment strategies is one of the main obstacles to developing cancer inhibitors. Up to now, various classes of therapeutics have been developed to inhibit cancer progression. Peptides due to their small size and easy production compared to proteins are highly regarded in designing cancer vaccines and oncogenic pathway inhibitors. Although peptides seem to be a suitable therapeutic option, their short lifespan, instability, and low binding affinity for their target have not been widely applicable against malignant tumors. Given the peptides' disadvantages, a new class of agents called peptidomimetic has been introduced. With advances in physical chemistry and biochemistry, as well as increased knowledge about biomolecule structures, it is now possible to chemically modify peptides to develop efficient peptidomimetics. In recent years, numerous studies have been performed to the evaluation of the effectiveness of peptidomimetics in inhibiting metastasis, angiogenesis, and cancerous cell growth. Here, we offer a comprehensive review of designed peptidomimetics to diagnose and treat cancer.

Citing Articles

Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.

Xiao W, Jiang W, Chen Z, Huang Y, Mao J, Zheng W Signal Transduct Target Ther. 2025; 10(1):74.

PMID: 40038239 PMC: 11880366. DOI: 10.1038/s41392-024-02107-5.

New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.

Nada H, Choi Y, Kim S, Jeong K, Meanwell N, Lee K Signal Transduct Target Ther. 2024; 9(1):341.

PMID: 39638817 PMC: 11621763. DOI: 10.1038/s41392-024-02036-3.

Development and Prospects of Furin Inhibitors for Therapeutic Applications.

Ivachtchenko A, Khvat A, Shkil D Int J Mol Sci. 2024; 25(17).

PMID: 39273149 PMC: 11394684. DOI: 10.3390/ijms25179199.

Peptoids: Smart and Emerging Candidates for the Diagnosis of Cancer, Neurological and Autoimmune Disorders.

Giorgio A, Del Gatto A, Pennacchio S, Saviano M, Zaccaro L Int J Mol Sci. 2023; 24(22).

PMID: 38003529 PMC: 10671428. DOI: 10.3390/ijms242216333.

Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era.

Rossino G, Marchese E, Galli G, Verde F, Finizio M, Serra M Molecules. 2023; 28(20).

PMID: 37894644 PMC: 10609221. DOI: 10.3390/molecules28207165.

References

Sidman R, Li J, Lawrence M, Hu W, Musso G, Giordano R . The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease. Sci Transl Med. 2015; 7(309):309ra165. PMC: 4787616. DOI: 10.1126/scitranslmed.aac4882. View

Haubner R, Wester H, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman S . Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001; 42(2):326-36. View

Irby R, Yeatman T . Role of Src expression and activation in human cancer. Oncogene. 2000; 19(49):5636-42. DOI: 10.1038/sj.onc.1203912. View

Bodero L, Lopez Rivas P, Korsak B, Hechler T, Pahl A, Muller C . Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting. Beilstein J Org Chem. 2018; 14:407-415. PMC: 5827777. DOI: 10.3762/bjoc.14.29. View

Tsubamoto M, Khanh Le T, Li M, Watanabe T, Matsumi C, Parvatkar P . A Guanidyl-Based Bivalent Peptidomimetic Inhibits K-Ras Prenylation and Association with c-Raf. Chemistry. 2019; 25(59):13531-13536. DOI: 10.1002/chem.201903129. View

Childs-Disney J, Tsitovich P, Disney M . Using modularly assembled ligands to bind RNA internal loops separated by different distances. Chembiochem. 2011; 12(14):2143-6. PMC: 3378996. DOI: 10.1002/cbic.201100298. View

Gomari M, Saraygord-Afshari N, Farsimadan M, Rostami N, Aghamiri S, Farajollahi M . Opportunities and challenges of the tag-assisted protein purification techniques: Applications in the pharmaceutical industry. Biotechnol Adv. 2020; 45:107653. DOI: 10.1016/j.biotechadv.2020.107653. View

Ghiotto F, Fais F, Tenca C, Tomati V, Morabito F, Casciaro S . Apoptosis of B-cell chronic lymphocytic leukemia cells induced by a novel BH3 peptidomimetic. Cancer Biol Ther. 2009; 8(3):263-71. DOI: 10.4161/cbt.8.3.7424. View

Schlomann U, Koller G, Conrad C, Ferdous T, Golfi P, Garcia A . ADAM8 as a drug target in pancreatic cancer. Nat Commun. 2015; 6:6175. PMC: 5014123. DOI: 10.1038/ncomms7175. View

10.

Wang Y, Patel B, Anreddy N, Zhang Y, Zhang G, Alqahtani S . Thiazole-valine peptidomimetic (TTT-28) antagonizes multidrug resistance in vitro and in vivo by selectively inhibiting the efflux activity of ABCB1. Sci Rep. 2017; 7:42106. PMC: 5299601. DOI: 10.1038/srep42106. View

11.

Bansal R, Prakash J, de Ruiter M, Poelstra K . Targeted recombinant fusion proteins of IFNγ and mimetic IFNγ with PDGFβR bicyclic peptide inhibits liver fibrogenesis in vivo. PLoS One. 2014; 9(2):e89878. PMC: 3933682. DOI: 10.1371/journal.pone.0089878. View

12.

Schlessinger J . New roles for Src kinases in control of cell survival and angiogenesis. Cell. 2000; 100(3):293-6. DOI: 10.1016/s0092-8674(00)80664-9. View

13.

Evans B, King A, Katsifis A, Matesic L, Jamie J . Methods to Enhance the Metabolic Stability of Peptide-Based PET Radiopharmaceuticals. Molecules. 2020; 25(10). PMC: 7287708. DOI: 10.3390/molecules25102314. View

14.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

15.

Wilkinson-Berka J, Deliyanti D . The potential of anti-VEGF (Vasotide) by eye drops to treat proliferative retinopathies. Ann Transl Med. 2016; 4(Suppl 1):S41. PMC: 5104608. DOI: 10.21037/atm.2016.10.27. View

16.

Qvit N, Rubin S, Urban T, Mochly-Rosen D, Gross E . Peptidomimetic therapeutics: scientific approaches and opportunities. Drug Discov Today. 2016; 22(2):454-462. PMC: 5759319. DOI: 10.1016/j.drudis.2016.11.003. View

17.

Ferber S, Tiram G, Sousa-Herves A, Eldar-Boock A, Krivitsky A, Scomparin A . Co-targeting the tumor endothelium and P-selectin-expressing glioblastoma cells leads to a remarkable therapeutic outcome. Elife. 2017; 6. PMC: 5644959. DOI: 10.7554/eLife.25281. View

18.

Sirotnak F, Sepp-Lorenzino L, Kohl N, Rosen N, Scher H . A peptidomimetic inhibitor of ras functionality markedly suppresses growth of human prostate tumor xenografts in mice. Prospects for long-term clinical utility. Cancer Chemother Pharmacol. 2000; 46(1):79-83. DOI: 10.1007/s002800000126. View

19.

Wang X, Su H, Wang W, Chen C, Cao X . Peptidomimetics Based On Dehydroepiandrosterone Scaffold: Synthesis, Antiproliferation Activity, Structure-Activity Relationship, and Mechanisms. Sci Rep. 2016; 6:32654. PMC: 5009342. DOI: 10.1038/srep32654. View

20.

Dal Corso A, Caruso M, Belvisi L, Arosio D, Piarulli U, Albanese C . Synthesis and biological evaluation of RGD peptidomimetic-paclitaxel conjugates bearing lysosomally cleavable linkers. Chemistry. 2015; 21(18):6921-9. DOI: 10.1002/chem.201500158. View