Cysteine racemization during the Fmoc solid phase peptide synthesis of the Nav1.7-selective peptide - protoxin II

Journal of Peptide Science

Volumn 18, Issue 7, 2012, Pages 442-448

  Park, Jae H ^a   Carlin, Kevin P ^a   Wu, Gang ^a   Ilyin, Victor I ^a   Kyle, Donald J ^a  

^a Purdue Pharma Discovery Research   (United States)

Author keywords

2,4,6 collidine; Air oxidation; Electrophysiology; GrTx I; GsAF I; GsAF II; GsMTx II; JzTx V; JzTx XII; Nav1.7; ND7 23; Patch clamp; PaTx I; PaTx II; ProTx II; VsTx II

Indexed keywords

BASE; CYSTEINE; MORPHOLINE DERIVATIVE; PROTOXIN; PROTOXIN 2; SODIUM CHANNEL NAV1.2; SODIUM CHANNEL NAV1.7; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYSTINE KNOT MOTIF; ELECTROPHYSIOLOGY; HUMAN; HUMAN CELL; METHODOLOGY; NONHUMAN; OXIDATION; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN PURIFICATION; RACEMIZATION; SOLID PHASE SYNTHESIS; STANDARD;

CELL LINE; CYSTEINE; HUMANS; MORPHOLINES; NAV1.7 VOLTAGE-GATED SODIUM CHANNEL; OXIDATION-REDUCTION; PEPTIDES; SODIUM CHANNEL BLOCKERS; SOLID-PHASE SYNTHESIS TECHNIQUES; SPIDER VENOMS; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

EID: 84862631617     PISSN: 10752617     EISSN: 10991387     Source Type: Journal    
DOI: 10.1002/psc.2407     Document Type: Article

References (36)

1. Fischer TZ, Waxman SG. Familial pain syndromes from mutations of the NaV1.7 sodium channel. Ann. N. Y. Acad. Sci. 2010; 1184: 196-207.
2. Herzog RI, Cummins TR, Ghassemi F, Dib-Hajj SD, Waxman SG. Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J. Physiol. 2003; 551: 741-750.
3. Choi JS, Waxman SG. Physiological interactions between Nav1.7 and Nav1.8 sodium channels: a computer simulation study. J. Neurophysiol. 2011; 106: 3173-3184.
4. Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH, Wood JN. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 12706-12711.
5. Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444: 894-898.
6. Middleton RE, Warren VA, Kraus RL, Hwang JC, Liu CJ, Dai G, Brochu RM, Kohler MG, Gao YD, Garsky VM, Borusky MJ, Mehl JT, Cohen CJ, Smith MM. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry 2002; 41: 14734-14747.
7. Schmalhofer WA, Calhoun J, Burrows R, Bailey T, Kohler MG, Weinglass AB, Kaczorowski GJ, Garcia ML, Koltzenburg M, Priest BT. ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors. Mol. Pharmacol. 2008; 74: 1476-1484.
8. Pallaghy PK, Nielsen KJ, Craik DJ, Norton RS. A common structural motif incorporating a cystine knot and a triple-stranded beta-sheet in toxic and inhibitory polypeptides. Protein Sci. 1994; 10: 1833-1839.
9. Angell Y, Han Y, Albericio F, Barany, G. Minimization of cysteine racemization during stepwise solid-phase peptide synthesis. In Peptides: Frontiers of Peptide Science (Proceedings of the 15th American Peptide Symposium), Tam JP and Kaumaya PTP (eds.). Kluwer: Dordrecht, The Netherlands, 2002; 339-340.
10. Han Y, Albericio F, Barany G. Occurrence and minimization of cysteine racemization during stepwise solid-phase peptide synthesis. J. Org. Chem. 1997; 62: 4307-4312.
11. Loidl G, Dick F, Mergler M, Schoenleber RO. Optimized coupling protocols for the incorporation of Cys derivatives during Fmoc-SPPS. Adv. Exp. Med. Biol. 2009; 611: 163-164.
12. Angell YM, Alsina J, Baranu G, Albericio F. Practical protocols for stepwise solid-phase synthesis of cysteine-containing peptides. J. Pept. Res. 2002; 60: 292-299.
13. Kaiser T, Nicholson GJ, Kohlbau HK, Voelter W. Racemization studies of Fmoc-Cys(Trt)-OH during stepwise Fmoc-solid phase peptide synthesis. Tetrahedron Lett. 1996; 37: 1187-1190.
14. Musiol HJ, Siedler F, Quarzago D, Moroder L. Redox-active bis-cysteinyl peptides. I. Synthesis of cyclic cystinyl peptides by conventional methods in solution and on solid supports. Biopolymers 1994; 34: 1553-1562.
15. Frare E, de Laureto PP, Scaramella E, Tonello F, Marin O, Deana R, Fontana A. Chemical synthesis of the RGD-protein decorsin: Pro → Ala replacement reduces protein thermostability. Protein Eng. Des. Sel. 2005; 18: 487-495.
16. +-channel blocker from the scorpion. Tityus cambridgei. Protein Sci. 2002; 11: 390-400.
17. 1H NMR structure, and activity of a three-disulfide-bridged maurotoxin analog designed to restore the consensus motif of scorpion toxins. J. Biol. Chem. 2000; 275: 13605-13612.
18. Savarin P, Romi-Lebrun R, Zinn-Justin S, Lebrun B, Nakajima T, Gilquin B, Menez A. Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1. Protein Sci. 1999; 8: 2672-2685.
19. De-Laureto PP, Scaramella E, De Filippis V, Marin O, Doni MG, Fontana A. Chemical synthesis and structural characterization of the RGD-protein decorsin: a potent inhibitor of platelet aggregation. Protein Sci. 1998; 7: 433-444.
20. Sabatier JM, Lecomte C, Mabrouk K, Darbon H, Oughideni R, Canarelli S, Rochat H, Martin-Eauclaire MF, van Rietschoten J. Synthesis and characterization of leiurotoxin I analogs lacking one disulfide bridge: evidence that disulfide pairing 3-21 is not required for full toxin activity. Biochemistry 1996; 35: 10641-10647.
21. Juirou B, Mosbah A, Visan V, Grissmer S, M'Barek S, Fajloun Z, Van Rietschoten J, Devaux C, Rochat H, Lippens G, El Ayeb M, De Waard M, Mabrouk K, Sabatier JM. Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels. Biochem. J. 2004; 377: 37-49.
22. Zamborelli TJ, Dodson WS, Harding BJ, Zhang J, Bennett BD, Lenz DM, Young Y, Haniu M, Liu CF, Jones T, Jarosinski MA. A comparison of folding techniques in the chemical synthesis of the epidermal growth factor-like domain in neu differentiation factor alpha/beta. J. Pept. Res. 2000; 55: 359-371.
23. Smith JJ, Cummins TR, Alphy S, Blumenthal KM. Molecular interactions of the gating modifier toxin ProTx-II with NaV1.5: implied existence of a novel toxin binding site coupled to activation. J. Biol. Chem. 2007; 282: 12687-12697.
24. Steiner AM, Bulaj G. Optimization of oxidative folding methods for cysteine-rich peptides: a study of conotoxins containing three disulfide bridges. J. Pept. Sci. 2011; 17: 1-7.
25. Edgerton GB, Blumenthal KM, Hanck DA. Evidence for multiple effects of ProTxII on activation gating in Na(V)1.5. Toxicon 2008; 52: 489-500.
26. Sokolov S, Kraus RL, Scheuer T, Catterall WA. Inhibition of sodium channel gating by trapping the domain II voltage sensor with protoxin II. Mol. Pharmacol. 2008; 73: 1020-1028.
27. Xiao Y, Blumenthal K, Jackson JO 2nd, Liang S. Cummins TR. The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation. Mol. Pharmacol. 2010; 78: 1124-1134.
28. Zeng XZ, Deng M, Lin Y, Yuan C, Pi J, Liang SP. Isolation and characterization of Jingzhaotoxin-V, a novel neurotoxin from the venom of the spider Chilobrachys jingzhao. Toxicon 2007; 49: 388-399. DOI: dx.doi.org.
29. Yuan C, Liao Z, Zeng X, Dai L, Kuang F, Liang S. Jingzhaotoxin-XII, a gating modifier specific for Kv4.1 channels. Toxicon 2007; 50: 646-652.
30. Lampe RA. U.S. Patent 5877026, 1999.
31. Lampe RA, Sachs F. U.S. Patent 5968838, 1999.
32. Ruta V, MacKinnon R. Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry 2004; 43: 10071-10079.
33. Clement H, Odell G, Zamudio FZ, Redaelli E, Wanke E, Alagon A, Possani LD. Isolation and characterization of a novel toxin from the venom of the spider Grammostola rosea that blocks sodium channels. Toxicon 2007; 50: 65-74.
34. Chagot B, Escoubas P, Villegas E, Bernard C, Ferrat G, Corzo G, Lazdunski M, Darbon H. Solution structure of Phrixotoxin 1, a specific peptide inhibitor of Kv4 potassium channels from the venom of the theraphosid spider Phrixotrichus auratus. Protein Sci. 2004; 13: 1197-1208.
35. Oswald RE, Suchyna TM, McFeeters R, Gottlieb PA, Sachs F. Solution structure of peptide toxins that block mechanosensitive ion channels. J. Biol. Chem. 2002; 277: 34443-34450.
36. Diochot S, Drici MD, Moinier D, Fink M, Lazdunski M. Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Ito1 in cardiac electrogenesis. Br. J. Pharmacol. 1999; 126: 251-263.