Rational Design of Hybrid Peptides: A Novel Drug Design Approach

Overview

Journal Curr Med Sci

Specialty General Medicine

Date 2019 Jun 19

PMID 31209802

Citations 14

Authors

Chao Wang

Chen Yang

Yu-Chen Chen

Liang Ma

Kun Huang

Affiliations

Soon will be listed here.

Abstract

Peptides play crucial roles in various physiological and pathological processes. Consequently, the investigation of peptide-based drugs is a highlight in the research and development of new drugs. However, natural peptides are not always ideal choices for clinical application due to their limited number and sometimes cytotoxicity to normal cells. Aiming to gain stronger or specific or novel biological effects and overcome the disadvantages of natural peptides, artificial hybrid peptides have been designed by combining the sequence of two or more different peptides with varied biological functions. Compared to natural peptides, hybrid peptides have shown better therapeutic potentials against bacteria, tumors, and metabolic diseases. In this review, design strategies, structure features and recent development of hybrid peptides are summarized; future directions for the research and development of hybrid peptide drugs are also discussed.

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References

Ellerby H, Arap W, Ellerby L, Kain R, Andrusiak R, Rio G . Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med. 1999; 5(9):1032-8. DOI: 10.1038/12469. View

Hancock R, Scott M . The role of antimicrobial peptides in animal defenses. Proc Natl Acad Sci U S A. 2000; 97(16):8856-61. PMC: 34023. DOI: 10.1073/pnas.97.16.8856. View

Chen Y, Xu X, Hong S, Chen J, Liu N, Underhill C . RGD-Tachyplesin inhibits tumor growth. Cancer Res. 2001; 61(6):2434-8. View

Yeaman M, Yount N . Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev. 2003; 55(1):27-55. DOI: 10.1124/pr.55.1.2. View

Runge S, Gram C, Brauner-Osborne H, Madsen K, Knudsen L, Wulff B . Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus. J Biol Chem. 2003; 278(30):28005-10. DOI: 10.1074/jbc.M301085200. View

Papo N, Shai Y . New lytic peptides based on the D,L-amphipathic helix motif preferentially kill tumor cells compared to normal cells. Biochemistry. 2003; 42(31):9346-54. DOI: 10.1021/bi027212o. View

DU VIGNEAUD V, RESSLER C, TRIPPETT S . The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. J Biol Chem. 1953; 205(2):949-57. View

DAVIDSON I, SALTER J, BEST C . Calorigenic action of glucagon. Nature. 1957; 180(4595):1124. DOI: 10.1038/1801124a0. View

Lee D, Park Y, Jin I, Hahm K, Lee H, Moon Y . Structure-antiviral activity relationships of cecropin A-magainin 2 hybrid peptide and its analogues. J Pept Sci. 2004; 10(5):298-303. DOI: 10.1002/psc.504. View

10.

Reddy K, Yedery R, Aranha C . Antimicrobial peptides: premises and promises. Int J Antimicrob Agents. 2004; 24(6):536-47. DOI: 10.1016/j.ijantimicag.2004.09.005. View

11.

Nasongkla N, Shuai X, Ai H, Weinberg B, Pink J, Boothman D . cRGD-functionalized polymer micelles for targeted doxorubicin delivery. Angew Chem Int Ed Engl. 2004; 43(46):6323-7. DOI: 10.1002/anie.200460800. View

12.

Eckert R, Qi F, Yarbrough D, He J, Anderson M, Shi W . Adding selectivity to antimicrobial peptides: rational design of a multidomain peptide against Pseudomonas spp. Antimicrob Agents Chemother. 2006; 50(4):1480-8. PMC: 1426969. DOI: 10.1128/AAC.50.4.1480-1488.2006. View

13.

Eckert R, He J, Yarbrough D, Qi F, Anderson M, Shi W . Targeted killing of Streptococcus mutans by a pheromone-guided "smart" antimicrobial peptide. Antimicrob Agents Chemother. 2006; 50(11):3651-7. PMC: 1635210. DOI: 10.1128/AAC.00622-06. View

14.

He J, Anderson M, Shi W, Eckert R . Design and activity of a 'dual-targeted' antimicrobial peptide. Int J Antimicrob Agents. 2009; 33(6):532-7. PMC: 2696886. DOI: 10.1016/j.ijantimicag.2008.11.013. View

15.

Day J, Ottaway N, Patterson J, Gelfanov V, Smiley D, Gidda J . A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009; 5(10):749-57. DOI: 10.1038/nchembio.209. View

16.

Huang W, Lu L, Shao X, Tang C, Zhao X . Anti-melanoma activity of hybrid peptide P18 and its mechanism of action. Biotechnol Lett. 2009; 32(4):463-9. DOI: 10.1007/s10529-009-0175-2. View

17.

Horibe T, Kohno M, Haramoto M, Ohara K, Kawakami K . Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent. J Transl Med. 2011; 9:8. PMC: 3032679. DOI: 10.1186/1479-5876-9-8. View

18.

Tada N, Horibe T, Haramoto M, Ohara K, Kohno M, Kawakami K . A single replacement of histidine to arginine in EGFR-lytic hybrid peptide demonstrates the improved anticancer activity. Biochem Biophys Res Commun. 2011; 407(2):383-8. DOI: 10.1016/j.bbrc.2011.03.030. View

19.

Cheng B, Liu X, Gong H, Huang L, Chen H, Zhang X . Coffee components inhibit amyloid formation of human islet amyloid polypeptide in vitro: possible link between coffee consumption and diabetes mellitus. J Agric Food Chem. 2011; 59(24):13147-55. DOI: 10.1021/jf201702h. View

20.

Yang L, Horibe T, Kohno M, Haramoto M, Ohara K, Puri R . Targeting interleukin-4 receptor α with hybrid peptide for effective cancer therapy. Mol Cancer Ther. 2011; 11(1):235-43. DOI: 10.1158/1535-7163.MCT-11-0363. View