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Peptide β-Bend and 3 10 -Helix: from 3D-Structural Studies to Applications as Templates

Abstract

The 3 10-helix is a relatively common secondary structure motif in peptides and proteins. Its building block is one of various types of β-bend conformation which comprises an N α-acylated dipeptide alkylamide system. A complete 3D-structural characterization of this ternary helix has been achieved, thus allowing its unambiguous discrimination from the closely related α-helix. Recent applications of rigidified peptide β-bends and 3 10-helices as templates for investigations in synthetic organic chemistry (macrocyclization, catalysis), host–guest chemistry (molecular recognition), and physical chemistry (donor–acceptor interaction) will be discussed.

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Abbreviations

Ac:

acetyl

Agl:

Cα-allylglycine

Aib:

α-aminoisobutyric acid (or Cα,α-dimethylglycine)

(αMe)Phg:

Cα-methyl, Cα-phenylglycine

(αMe)Val:

Cα-methyl valine

Api:

4-amino-4-carboxypiperidine

ATANP:

2-amino-3-[1-(1,4,7-triazacyclononane)] propanoic acid

Bin:

2′,1′:1,2;1′′,2′′:3,4-dinaphthcyclohepta-1,3-diene-6-amino-6-carboxylic acid

Boc:

tert-butyloxycarbonyl

Bpa:

para-benzoyl-phenylalanine

Bz:

benzoyl

DMSO:

dimethylsulfoxide

ESR:

electron spin resonance

Fmoc:

fluoren-9-ylmethyloxycarbonyl

hhMag:

homo-homo-Mag

hMag:

homo-Mag

Mag:

Cα-methyl, Cα-allylglycine

NHBzl:

benzylamino

NHMe:

methylamino

NHtBu:

tert-butylamino

OMe:

methoxy

OtBu:

tert-butoxy

pBrBz:

para-bromobenzoyl

Z:

benzyloxycarbonyl

RCM:

ring-closing metathesis

TEMPO:

2,2,6,6-tetramethylpiperidinyl-1-oxy

TOAC:

2,2,6,6-tetramethylpiperidine-1-oxy-4-amino-4-carboxylic acid

Tren:

tris-(2-aminoethyl)amine

References

  1. (a) C. Toniolo, F. Formaggio, M. Crisma, G. Valle, W.H.J. Boesten, H.E. Schoemaker, J. Kamphuis, P.A. Temussi, E.L. Becker, and G. Précigoux: Tetrahedron 49, (3641) ((1993)). (b) C. Toniolo, A. Bianco, F. Formaggio, M. Crisma, G.M. Bonora, E. Benedetti, V. Del Duca, M. Saviano, B. Di Blasio, C. Pedone, and A. Aubry: Bioorg. Med. Chem. 3, 1211 (1995). (c) M. Crisma, A. Bianco, F. Formaggio, C. Toniolo, and J. Kamphuis: Lett. Pept. Sci. 2, 187 (1995)

  2. (a) C.M. Venkatachalam: Biopolymers 6, 1425 (1968). (b) C. Toniolo: CRC Crit. Rev. Biochem. 9, 1 (1980). (c) G.D. Rose, L.M. Gierasch, and J.A. Smith: Adv. Protein Chem. 37, 1 (1985)

  3. (a) C. Toniolo and E. Benedetti: Trends Biochem. Sci. 16, 350 (1991). (b) D.J. Barlow and J.M. Thornton: J. Mol. Biol. 201, 601 (1988). (c) I.L. Karle and P. Balaram: Biochemistry 29, 6747 (1990). (d) M.E. Karpen, P.L. de Haseth, and K.E. Neet: Protein Sci. 1, 1333 (1992). (e) G.L. Millhauser: Biochemistry 34, 3873 (1995). (f) K.A. Bolin and G.L. Millhauser: Acc. Chem. Res. 32, 1027 (1999). (g) L. Pal and G. Basu: Protein Eng. 12, 811 (1999). (h) L. Pal, G. Basu, and P. Chakrabarti: Proteins: Struct. Funct. Genet. 48, 571 (2002). (i) L. Pal, P. Chakrabarti, and G. Basu: J. Mol. Biol. 326, 273 (2003)

  4. (a) E. Benedetti, A. Bavoso, B. Di Blasio, V. Pavone, C. Pedone, C. Toniolo, and G.M. Bonora: Proc. Natl. Acad. Sci. USA 79, 7951 (1982). (b) R. Nagaraj and P. Balaram: Acc. Chem. Res. 14, 356 (1981). (c) S. Rebuffat, C. Goulard, B. Bodo, and M.-F. Roquebert: Recent Res. Devel. Org. Biorg. Chem. 3, 65 (1999). (d) C. Toniolo, M. Crisma, F. Formaggio, C. Peggion, A.F. Epand, and R.M. Epand: Cell. Mol. Life Sci. 58, 1179 (2001). (e) C. Peggion, F. Formaggio, M. Crisma, R.F. Epand, R.M. Epand, and C. Toniolo: J. Pept. Sci.9, 679 (2003)

  5. H.S. Taylor (1941) Proc. Am. Phyl. Soc. 85 1 Occurrence Handle1:CAS:528:DyaH38XhtFKlug%3D%3D

    CAS  Google Scholar 

  6. L. Pauling R.B. Corey H.R. Branson (1951) Proc. Natl. Acad. Sci. USA 37 205 Occurrence Handle1:CAS:528:DyaG3MXktVCqtg%3D%3D Occurrence Handle14816373

    CAS  PubMed  Google Scholar 

  7. L. Bragg J.C. Kendrew M.F. Perutz (1950) Proc. R. Soc. London A 203 321

    Google Scholar 

  8. (a) V. Pavone, G. Gaeta, A. Lombardi, F. Nastri, O. Maglio, C. Isernia, and M. Saviano: Biopolymers 38, 705 (1996). (b) R.T. Wintjens, M.J. Rooman, and S.J. Wodak: J. Mol. Biol. 255, 235 (1996). (c) K.-L. Chou: Biopolymers 42, 837 (1997). (d) C. Ramakrishnan and D.V. Nataraj: J. Pept. Sci. 4, 239 (1998)

  9. (a) M.L. Huggins: Chem. Rev. 32, 195 (1943). (b) J. Donohue: Proc. Natl. Acad. Sci. USA 39, 470 (1953). (c) G.N. Ramachandran, C.M. Venkatachalam, and S. Krimm: Biophys. J. 66, 849 (1966). (d) E.N. Baker and R.E. Hubbard: Progr. Biophys. Mol. Biol. 44, 97 (1984)

  10. (a) M. Marino, L. Braun, P. Cossart, and P. Ghosh: Mol. Cell. 4, 1063 (1999). (b) M. Marino, L. Braun, P. Cossart, and P. Ghosh: Proc. Natl. Acad. Sci. USA 4, 8784 (2000). (c) J.W. Peters, M.H.B. Stowell, and D.C. Rees: Nature: Struct. Biol. 3, 991 (1996). (d) B. Kobe: Nature: Struct. Biol. 3, 977 (1996). (e) B. Kobe and A.V. Kajava: Trends Biochem. Sci. 25, 509 (2000). (f) B. Kobe and A.V. Kajava: Curr. Opin. Struct. Biol. 11, 725 (2001). (g) A.V. Kajava and B. Kobe: Protein Sci. 11, 1082 (2002)

  11. G.R. Marshall: In N. Kharasch (ed.), Intra-Science Chemistry Report (Vol. 5), Gordon and Breach (1971), pp. 305–316

  12. (a) N. Shamala, R. Nagaraj, and P. Balaram: J. Chem. Soc., Chem. Commun. 996 (1978). (b) C. Toniolo, M. Crisma, F. Formaggio, and C. Peggion: Biopolymers (Pept. Sci.) 60, 396 (2001)

  13. (a) V. Pavone, B. Di Blasio, A. Santini, E. Benedetti, C. Pedone, C. Toniolo, and M. Crisma: J. Mol. Biol. 214, 633 (1990). (b) C. Toniolo, M. Crisma, G.M. Bonora, E. Benedetti, B. Di Blasio, V. Pavone, C. Pedone, and A. Santini: Biopolymers 31, 129 (1991). (c) R. Gessmann, H. Brueckner, and K. Petratos: J. Pept. Sci. 9, 753 (2003)

  14. (a) M. Goodman, C. Toniolo, and P. Pallai: In B. Castro and J. Martinez (eds.), Forum Peptides, Dohr (1985), pp. 146-174. (b) V. Pavone, E. Benedetti, B. Di Blasio, C. Pedone, A. Santini, A. Bavoso, C. Toniolo, M. Crisma, and L. Sartore: J. Biomol. Struct. Dyn. 7, 1321 (1990). (c) G.R. Marshall, E.E. Hodgkin, D.A. Langs, G.D. Smith, J. Zabrocki, and M.T. Leplawy: Proc. Natl. Acad. Sci. USA 87, 487 (1990). (d) K. Okuyama, N. Tanaka, M. Doi, and M. Narita: Bull. Chem. Soc. Jpn. 61, 3115 (1988)

  15. C. Toniolo E. Benedetti (1991) Macromolecules 24 4004 Occurrence Handle10.1021/ma00014a006 Occurrence Handle1:CAS:528:DyaK3MXkt12rt7w%3D

    Article  CAS  Google Scholar 

  16. (a) C. Toniolo, G.M. Bonora, V. Barone, A. Bavoso, E. Benedetti, B. Di Blasio, P. Grimaldi, F. Lelj, V. Pavone, and C. Pedone: Macromolecules 18, 895 (1985). (b) D.F. Kennedy, M. Crisma, C. Toniolo, and D. Chapman: Biochemistry 30, 6541 (1991). (c) G. Yoder, A. Polese, R.A.G.D. Silva, F. Formaggio, M. Crisma, Q.B. Broxterman, J. Kamphuis, C. Toniolo, and T.A. Keiderling: J. Am. Chem. Soc. 119, 10278 (1997). (d) C. Toniolo, A. Polese, F. Formaggio, M. Crisma, and J. Kamphuis: J. Am. Chem. Soc. 118, 2744 (1996). (e) F. Formaggio, M. Crisma, P. Rossi, P. Scrimin, B. Kaptein, Q.B. Broxterman, J. Kamphuis and C. Toniolo: Chem. Eur. J. 6, 4498 (2000). (f) R. Gratias, R. Konat, H. Kessler, M. Crisma, G. Valle, A. Polese, F. Formaggio, C. Toniolo, Q.B. Broxterman, and J. Kamphuis: J. Am. Chem. Soc. 120, 4763 (1998). (g) S. Mammi, M. Rainaldi, M. Bellanda, E. Schievano, E. Peggion, Q.B. Broxterman, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 122, 11735 (2000)

    Google Scholar 

  17. (a) F. Donald, G. Hungerford, D.J.S. Birch, and B.D. Moore: Chem. Commun. 313 (1995). (b) G. Hungerford, M. Martinez-Insua, D.J.S. Birch, and B.D. Moore: Angew. Chem. Int. Ed. Engl. 37, 326 (1998). (c) P. Pengo, L. Pasquato, S. Moro, A. Brigo, F. Fogolari, Q.B. Broxterman, B. Kaptein, and P. Scrimin: Angew. Chem. Int. Ed. 42, 3388 (2003)

  18. (a) C.E. Schafmeister, J. Po, and G.L. Verdine: J. Am. Chem. Soc. 122, 5891 (2000). (b) H.E. Blackwell and J.H. Grubbs: Angew. Chem. Int. Ed. Engl. 37, 3281 (1998). (c) H.E. Blackwell, J.S. Sadowski, R.J. Howard, J.N. Sampson, J.A. Chao, W.E. Steinmetz, D.J. O’ Leary, and R.H. Grubbs: J. Org. Chem. 66, 5291 (2001). (d) S.J. Miller, H.E. Blackwell, and R.H. Grubbs: J. Am. Chem. Soc. 118, 9606 (1996). (e) B. Kaptein, Q.B. Broxterman, H.E. Schoemaker, F.P.J.T. Rutjes, J.J.N. Veerman, J. Kamphuis, C. Peggion, F. Formaggio, and C. Toniolo: Tetrahedron 57, 6567 (2001). (f) J. Pernerstorfer, M. Schuster, and S. Blechert: J. Chem. Soc., Chem. Commun. 1949 (1997). (g) A. Ravi, B.V. Venkataram Prasad, and P. Balaram: J. Am. Chem. Soc. 105, 105 (1983). (h) M. Saviano, E. Benedetti, R.M. Vitale, B. Kaptein, Q.B. Broxterman, M. Crisma, F. Formaggio, and C. Toniolo: Macromolecules 35, 4204 (2002)

  19. F. Formaggio M. Bonchio M. Crisma C. Peggion S. Mezzato A. Polese A. Barazza S. Antonello F. Maran Q.B. Broxterman B. Kaptein J. Kamphuis R.M. Vitale M. Saviano E. Benedetti C. Toniolo (2002) Chem. Eur. J. 8 84 Occurrence Handle10.1002/1521-3765(20020104)8:1<84::AID-CHEM84>3.0.CO;2-N Occurrence Handle1:CAS:528:DC%2BD38Xmt1ylsA%3D%3D

    Article  CAS  Google Scholar 

  20. (a) S.J. Miller, G.T. Copeland, N. Papaioannou, T.E. Horstmann, and E.M. Ruel: J. Am. Chem. Soc. 120, 1629 (1998). (b) G.T. Copeland, E.R. Jarvo, and S.J. Miller: J. Org. Chem. 63, 6784 (1998). (c) G.T. Copeland and S.J. Miller: J. Am. Chem. Soc. 121, 4306 (1999). (d) E.R. Jarvo, G.T. Copeland, N. Papaioannou, P.J. Bonitatebus, Jr., and S.J. Miller: J. Am. Chem. Soc. 121, 11638 (1999). (e) R.F. Harris, A.J. Nation, G.T. Copeland, and S.J. Miller: J. Am. Chem. Soc. 122, 11270 (2000). (f) J.T. Blank, D.J. Guerin, and S.J. Miller:Org. Lett. 2, 1247 (2000). (g) E.R. Jarvo, M.M. Vasbinder, and S.J. Miller: Tetrahedron 56, 9773 (2000). (h) M.M. Vasbinder, E.R. Jarvo, and S.J. Miller: Angew. Chem. Int. Ed. 40, 2824 (2001). (i) G.T. Copeland and S.J. Miller: J. Am. Chem. Soc. 123, 6496 (2001). (j) E.R. Jarvo, C.A. Evans, G.T. Copeland, and S.J. Miller: J. Org. Chem. 66, 5522 (2001)

  21. (a) P. Rossi, F. Felluga, P. Tecilla, F. Formaggio, M. Crisma, C. Toniolo, and P. Scrimin: J. Am. Chem. Soc. 121, 6948 (1999). (b) P. Rossi, F. Felluga, P. Tecilla, F. Formaggio, M. Crisma, C. Toniolo, and P. Scrimin: Biopolymers (Pept. Sci.) 55, 496 (2000). (c) C. Sissi, P. Rossi, F. Felluga, F. Formaggio, M. Palumbo, P. Tecilla, C. Toniolo, and P. Scrimin: J. Am. Chem. Soc. 123, 3169 (2001). (d) A. Scarso, U. Scheffer, M. Göbel, Q.B. Broxterman, B. Kaptein, F. Formaggio, C. Toniolo, and P. Scrimin: Proc. Natl. Acad. Sci. USA 99, 5144 (2002)

    Google Scholar 

  22. (a) M. Maggini, G. Scorrano, A. Bianco, and C. Toniolo: J. Chem. Soc., Chem. Commun. 305 (1994). (b) A. Bianco, F. Gasparrini, M. Maggini, D. Misiti, A. Polese, M. Prato, G. Scorrano, C. Toniolo, and C. Villani: J. Am. Chem. Soc. 119, 7550 (1997). (c) A. Bianco, C. Corvaja, M. Crisma, D.M. Guldi, M. Maggini, E. Sartori, and C. Toniolo: Chem. Eur. J. 8, 1544 (2002). (d) S.H. Friedman, D.L. De Camp, R.P. Sijbesma, G. Srdanov, F. Wudl, and G.L. Kenyon: J. Am. Chem. Soc. 115, 6506 (1993). (e) A. Bianco, T. Da Ros, M. Prato, and C. Toniolo: J. Pept. Sci. 7, 208 (2001)

    Google Scholar 

  23. (a) C. Toniolo, M. Crisma, and F. Formaggio: Biopolymers (Pept. Sci.) 47, 153 (1998). (b) C. Toniolo, E. Valente, F. Formaggio, M. Crisma, G. Pilloni, C. Corvaja, A. Toffoletti, G.V. Martinez, M.P. Hanson, G.L. Millhauser, C. George and J.L. Flippen-Anderson:J. Pept. Sci. 1, 45 (1995). (c) P. Hanson, G. Martinez, G. Millhauser, F. Formaggio, M. Crisma, C. Toniolo, and C. Vita: J. Am. Chem. Soc. 118, 271 (1996). (d) P. Hanson, G. Millhauser, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 118, 7618 (1996). (e) P. Hanson, D.J. Anderson, G. Martinez, G. Millhauser, F. Formaggio, M. Crisma, C. Toniolo, and C. Vita: Mol. Phys. 95, 957 (1998). (f) V. Monaco, F. Formaggio, M. Crisma, C. Toniolo, P. Hanson, G. Millhauser, C. George, J.R. Deschamps, and J.L. Flippen-Anderson: Bioorg. Med. Chem. 7, 119 (1999). (g) D.J. Anderson, P. Hanson, J. Mc Nulty, G. Millhauser, V. Monaco, F. Formaggio, M. Crisma, and C. Toniolo: J. Am. Chem. Soc. 121, 6919 (1999). (h) J.C. Mc Nulty, J.L. Silapie, M. Carnevali, C.T. Farrar, R.G. Griffin, F. Formaggio, M. Crisma, C. Toniolo, and G.L. Millhauser: Biopolymers(Pept. Sci.) 55, 479 (2000)

    Google Scholar 

  24. (a) C. Corvaja, E. Sartori, A. Toffoletti, F. Formaggio, M. Crisma, and C. Toniolo: Biopolymers (Pept. Sci.) 55, 486 (2000). (b) C. Corvaja, E. Sartori, A. Toffoletti, F. Formaggio, M. Crisma, C. Toniolo, J.-P. Mazaleyrat, and M. Wakselman: Chem. Eur. J. 6, 2775 (2000). (c) E. Sartori, A. Toffoletti, F. Rastrelli, C. Corvaja, A. Bettio, F. Formaggio, S. Oancea, and C. Toniolo: J. Phys. Chem. A107, 6905 (2003)

  25. (a) B. Pispisa, A. Palleschi, L. Stella, M. Venanzi, and C. Toniolo: J. Phys. Chem. B102, 7890 (1998). (b) C. Toniolo, F. Formaggio, M. Crisma, J.-P. Mazaleyrat, M. Wakselman, C. George, J.R. Deschamps, J.L. Flippen-Anderson, B. Pispisa, M. Venanzi, and A. Palleschi: Chem. Eur. J. 5, 2254 (1999). (c) B. Pispisa, L. Stella, M. Venanzi, A. Palleschi, F. Marchiori, A. Polese, and C. Toniolo: Biopolymers 53, 169 (2000). (d) B. Pispisa, C. Mazzuca, A. Palleschi, L. Stella, M. Venanzi, F. Formaggio, C. Toniolo, J.-P. Mazaleyrat, and M. Wakselman: J. Fluoresc. 13, 139 (2003). (e) B. Pispisa, C. Mazzuca, A. Palleschi, L. Stella, M. Venanzi, M. Wakselman, J.-P. Mazaleyrat, M. Rainaldi, F. Formaggio, and C. Toniolo: Chem. Eur. J. 9, 4084 (2003)

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Toniolo, C., Crisma, M., Formaggio, F. et al. Peptide β-Bend and 3 10 -Helix: from 3D-Structural Studies to Applications as Templates. J Incl Phenom Macrocycl Chem 51, 121–136 (2005). https://doi.org/10.1007/s10847-004-0912-z

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  • DOI: https://doi.org/10.1007/s10847-004-0912-z

Keywords

  • β-bend
  • catalysis
  • donor–acceptor interaction
  • 3 10-helix
  • host–guest chemistry
  • macrocyclization
  • peptide conformation
  • Cα-tetrasubstituted α-amino acids