Cystine knot peptide's properties and its applications for drug design and molecular engineering

DENG Yuchen; GU Jiawei; NIE Fei; XIAO Liang

doi:10.3969/j.issn.1006-0111.2016.06.001

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2016 > 34(6): 481-484,496

DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001

Citation:

DENG Yuchen, GU Jiawei, NIE Fei, XIAO Liang. Cystine knot peptide's properties and its applications for drug design and molecular engineering[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(6): 481-484,496. doi: 10.3969/j.issn.1006-0111.2016.06.001

Cystine knot peptide's properties and its applications for drug design and molecular engineering

doi: 10.3969/j.issn.1006-0111.2016.06.001

1.
No. 3 Student Team, Naval Clinical Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China
2.
No. 11 Student Team, Clinical Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China
3.
Department of Marine Biotechnology, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-10-30
Rev Recd Date: 2016-04-26

Abstract

The cystine knot (CK) motif comprises an internal ring formed by two disulfide bonds and their connecting backbone segments which is threaded by a third disulfide bond. It is present in peptides and proteins of a variety of species, including fungi, plants, marine molluscs, insects and spiders. CK polypeptide is one of the ideal model molecules for drug design and molecular engineering research because of its stable structure and variety of bioactivities. Here we summarized the main structural features of both inhibitor cystine knot (ICK) peptide and cyclic cystine knot (CCK) peptide, including primary sequence, topology, permutation, synthesis and folding characteristics, as well as its applications on drug design and molecular engineering.
- cystine knot,
- cyclic cystine knot,
- inhibitor cystine knot,
- Kalata B1

References

[1]	Mcdonald NQ, Hendrickson WA. A structural superfamily of growth factors containing a cystine knot motif[J]. Cell, 1993, 73(3):421-424.
[2]	Isaacs NW. Cystine knots[J]. Curr Opin Struct Biol, 1995, 5(3):391-395.
[3]	Park S, Stromstedt AA, Goransson U. Cyclotide structure-activity relationships:qualitative and quantitative approaches linking cytotoxic and anthelmintic activity to the clustering of physicochemical forces[J]. PLoS One, 2014, 9(3):e91430.
[4]	Reinwarth M, Nasu D, Kolmar H, et al. Chemical synthesis, backbone cyclization and oxidative folding of cystine-knot peptides:promising scaffolds for applications in drug design[J]. Molecules, 2012, 17(11):12533-12552.
[5]	Sato K, Yamaguchi Y, Ishida Y, et al. Roles of basic amino acid residues in the activity of μ-conotoxin GⅢA and GⅢB, peptide blockers of muscle sodium channels[J]. Chem Biol Drug Des, 2015, 85(4):488-493.
[6]	Green BR, Bulaj G, Norton RS. Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity[J]. Future Med Chem, 2014, 6(15):1677-1698.
[7]	Pallaghy PK, Norton RS,Nielsen KJ, et al. A common structural motif incorporating a cystine knot and a triple-stranded β-sheet in toxic and inhibitory polypeptides[J]. Protein Sci, 1994, 3(10):1833-1839.
[8]	Norton RS, Pallaghy PK. The cystine knot structure of ion channel toxins and related polypeptides[J]. Toxicon, 1998, 36(11):1573-1583.
[9]	Craik DJ, Daly NL, Waine C. The cystine knot motif in toxins and implications for drug design[J]. Toxicon, 2001, 39(1):43-60.
[10]	Schroeder CI, Nielsen KJ, Adams DA, et al. Effects of Lys2 to Ala2 substitutions on the structure and potency of ω-conotoxins MVⅡA and CVID[J]. Biopolymers, 2012, 98(4):345-356.
[11]	Almeida AM, Li R, Gellman SH. Parallel β-sheet secondary structure is stabilized and terminated by interstrand disulfide cross-linking[J]. J Am Chem Soc, 2012, 134(1):75-78.
[12]	Henriques ST, Huang YH, Chaousis S, et al. The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells[J]. Chem Biol, 2015, 22(8):1087-1097.
[13]	Skjeldal L, Gran L, Sletten K, et al. Refined structure and metal binding site of the kalata B1 peptide[J]. Arch Biochem Biophys, 2002, 399(2):142-148.
[14]	Ravipati AS, Henriques ST, Poth AG, et al. Lysine-rich cyclotides:a new subclass of circular knotted proteins from Violaceae[J]. ACS Chem Biol, 2015, 10(11):2491-2450.
[15]	Slazak B, Jacobsson E, Kuta E, et al. Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae)[J]. Phytochemistry, 2015, 117:527-536.
[16]	Reinwarth M, Glotzbach B, Tomaszowski M, et al. Oxidative folding of peptides with cystine-knot architectures:kinetic studies and optimization of folding conditions[J]. Chembiochem, 2013, 14(1):137-146.
[17]	Mao B. Topological chirality of proteins[J]. Protein Sci, 1993, 2(6):1057-1059.
[18]	Tang YQ, Yuan J, Osapay G, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins[J]. Science, 1999, 286(5439):498-502.
[19]	Kliemannel M, Weininger U, Balbach J, et al. Examination of the slow unfolding of pro-nerve growth factor argues against a loop threading mechanism for nerve growth factor[J]. Biochemistry, 2006, 45(11):3517-3524.
[20]	Daly NL, Craik DJ. Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1[J]. J Biol Chem, 2000, 275(25):19068-19075.
[21]	Olivera BM, Rivier J, Clark C, et al. Diversity of Conus neuropeptides[J]. Science, 1990, 249(4966):257-263.
[22]	Banerjee J, Gyanda R, Chang YP, et al. The chemical synthesis of alpha-conotoxins and structurally modified analogs with enhanced biological stability[J]. Methods Mol Biol, 2013, 1081:13-34.
[23]	Guo Y, Sun DM, Wang FL, et al. Diaminodiacid Bridges to Improve Folding and Tune the Bioactivity of Disulfide-Rich Peptides[J]. Angew Chem Int Ed Engl, 2015.
[24]	Cheneval O, Schroeder CI, Durek T, et al. Fmoc-based synthesis of disulfide-rich cyclic peptides[J]. J Org Chem, 2014, 79(12):5538-5544.
[25]	Poth AG, Colgrave ML, Philip R, et al. Discovery of cyclotides in the fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins[J]. ACS Chem Biol, 2011, 6(4):345-355.
[26]	Maciel IS, Azevedo VM, Pereira TC, et al. The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice[J]. Neuroscience, 2014, 277:794-805.
[27]	Datta A, Kundu P, Bhunia A. Designing potent antimicrobial peptides by disulphide linked dimerization and N-terminal lipidation to increase antimicrobial activity and membrane perturbation:Structural insights into lipopolysaccharide binding[J]. J Colloid Interface Sci, 2016, 461:335-345.
[28]	Ireland DC, Wang CK, Wilson JA, et al. Cyclotides as natural anti-HIV agents[J]. Biopolymers, 2008, 90(1):51-60.
[29]	Moore SJ, Leung CL, Norton HK, et al. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging[J]. PLoS One, 2013, 8(4):e60498.

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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Cystine knot peptide's properties and its applications for drug design and molecular engineering

1. No. 3 Student Team, Naval Clinical Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China

2. No. 11 Student Team, Clinical Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China

3. Department of Marine Biotechnology, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China

Received Date: 2015-10-30

Rev Recd Date: 2016-04-26

Key words:

Abstract: The cystine knot (CK) motif comprises an internal ring formed by two disulfide bonds and their connecting backbone segments which is threaded by a third disulfide bond. It is present in peptides and proteins of a variety of species, including fungi, plants, marine molluscs, insects and spiders. CK polypeptide is one of the ideal model molecules for drug design and molecular engineering research because of its stable structure and variety of bioactivities. Here we summarized the main structural features of both inhibitor cystine knot (ICK) peptide and cyclic cystine knot (CCK) peptide, including primary sequence, topology, permutation, synthesis and folding characteristics, as well as its applications on drug design and molecular engineering.

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Reference (29)

[1]	Mcdonald NQ, Hendrickson WA. A structural superfamily of growth factors containing a cystine knot motif[J]. Cell, 1993, 73(3):421-424.
[2]	Isaacs NW. Cystine knots[J]. Curr Opin Struct Biol, 1995, 5(3):391-395.
[3]	Park S, Stromstedt AA, Goransson U. Cyclotide structure-activity relationships:qualitative and quantitative approaches linking cytotoxic and anthelmintic activity to the clustering of physicochemical forces[J]. PLoS One, 2014, 9(3):e91430.
[4]	Reinwarth M, Nasu D, Kolmar H, et al. Chemical synthesis, backbone cyclization and oxidative folding of cystine-knot peptides:promising scaffolds for applications in drug design[J]. Molecules, 2012, 17(11):12533-12552.
[5]	Sato K, Yamaguchi Y, Ishida Y, et al. Roles of basic amino acid residues in the activity of μ-conotoxin GⅢA and GⅢB, peptide blockers of muscle sodium channels[J]. Chem Biol Drug Des, 2015, 85(4):488-493.
[6]	Green BR, Bulaj G, Norton RS. Structure and function of μ-conotoxins, peptide-based sodium channel blockers with analgesic activity[J]. Future Med Chem, 2014, 6(15):1677-1698.
[7]	Pallaghy PK, Norton RS,Nielsen KJ, et al. A common structural motif incorporating a cystine knot and a triple-stranded β-sheet in toxic and inhibitory polypeptides[J]. Protein Sci, 1994, 3(10):1833-1839.
[8]	Norton RS, Pallaghy PK. The cystine knot structure of ion channel toxins and related polypeptides[J]. Toxicon, 1998, 36(11):1573-1583.
[9]	Craik DJ, Daly NL, Waine C. The cystine knot motif in toxins and implications for drug design[J]. Toxicon, 2001, 39(1):43-60.
[10]	Schroeder CI, Nielsen KJ, Adams DA, et al. Effects of Lys2 to Ala2 substitutions on the structure and potency of ω-conotoxins MVⅡA and CVID[J]. Biopolymers, 2012, 98(4):345-356.
[11]	Almeida AM, Li R, Gellman SH. Parallel β-sheet secondary structure is stabilized and terminated by interstrand disulfide cross-linking[J]. J Am Chem Soc, 2012, 134(1):75-78.
[12]	Henriques ST, Huang YH, Chaousis S, et al. The Prototypic Cyclotide Kalata B1 Has a Unique Mechanism of Entering Cells[J]. Chem Biol, 2015, 22(8):1087-1097.
[13]	Skjeldal L, Gran L, Sletten K, et al. Refined structure and metal binding site of the kalata B1 peptide[J]. Arch Biochem Biophys, 2002, 399(2):142-148.
[14]	Ravipati AS, Henriques ST, Poth AG, et al. Lysine-rich cyclotides:a new subclass of circular knotted proteins from Violaceae[J]. ACS Chem Biol, 2015, 10(11):2491-2450.
[15]	Slazak B, Jacobsson E, Kuta E, et al. Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae)[J]. Phytochemistry, 2015, 117:527-536.
[16]	Reinwarth M, Glotzbach B, Tomaszowski M, et al. Oxidative folding of peptides with cystine-knot architectures:kinetic studies and optimization of folding conditions[J]. Chembiochem, 2013, 14(1):137-146.
[17]	Mao B. Topological chirality of proteins[J]. Protein Sci, 1993, 2(6):1057-1059.
[18]	Tang YQ, Yuan J, Osapay G, et al. A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins[J]. Science, 1999, 286(5439):498-502.
[19]	Kliemannel M, Weininger U, Balbach J, et al. Examination of the slow unfolding of pro-nerve growth factor argues against a loop threading mechanism for nerve growth factor[J]. Biochemistry, 2006, 45(11):3517-3524.
[20]	Daly NL, Craik DJ. Acyclic permutants of naturally occurring cyclic proteins. Characterization of cystine knot and beta-sheet formation in the macrocyclic polypeptide kalata B1[J]. J Biol Chem, 2000, 275(25):19068-19075.
[21]	Olivera BM, Rivier J, Clark C, et al. Diversity of Conus neuropeptides[J]. Science, 1990, 249(4966):257-263.
[22]	Banerjee J, Gyanda R, Chang YP, et al. The chemical synthesis of alpha-conotoxins and structurally modified analogs with enhanced biological stability[J]. Methods Mol Biol, 2013, 1081:13-34.
[23]	Guo Y, Sun DM, Wang FL, et al. Diaminodiacid Bridges to Improve Folding and Tune the Bioactivity of Disulfide-Rich Peptides[J]. Angew Chem Int Ed Engl, 2015.
[24]	Cheneval O, Schroeder CI, Durek T, et al. Fmoc-based synthesis of disulfide-rich cyclic peptides[J]. J Org Chem, 2014, 79(12):5538-5544.
[25]	Poth AG, Colgrave ML, Philip R, et al. Discovery of cyclotides in the fabaceae plant family provides new insights into the cyclization, evolution, and distribution of circular proteins[J]. ACS Chem Biol, 2011, 6(4):345-355.
[26]	Maciel IS, Azevedo VM, Pereira TC, et al. The spinal inhibition of N-type voltage-gated calcium channels selectively prevents scratching behavior in mice[J]. Neuroscience, 2014, 277:794-805.
[27]	Datta A, Kundu P, Bhunia A. Designing potent antimicrobial peptides by disulphide linked dimerization and N-terminal lipidation to increase antimicrobial activity and membrane perturbation:Structural insights into lipopolysaccharide binding[J]. J Colloid Interface Sci, 2016, 461:335-345.
[28]	Ireland DC, Wang CK, Wilson JA, et al. Cyclotides as natural anti-HIV agents[J]. Biopolymers, 2008, 90(1):51-60.
[29]	Moore SJ, Leung CL, Norton HK, et al. Engineering agatoxin, a cystine-knot peptide from spider venom, as a molecular probe for in vivo tumor imaging[J]. PLoS One, 2013, 8(4):e60498.

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Cystine knot peptide's properties and its applications for drug design and molecular engineering

doi: 10.3969/j.issn.1006-0111.2016.06.001

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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