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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jan;87(1):487–491. doi: 10.1073/pnas.87.1.487

Factors governing helical preference of peptides containing multiple alpha,alpha-dialkyl amino acids.

G R Marshall 1, E E Hodgkin 1, D A Langs 1, G D Smith 1, J Zabrocki 1, M T Leplawy 1
PMCID: PMC53289  PMID: 2296604

Abstract

The presence of multiple alpha,alpha-dialkyl amino acids such as alpha-methylalanine (alpha-aminoisobutyric acid, Aib) leads to predominantly helical structures, either with alpha-helical or 3(10)-helical hydrogen bonding patterns. The crystal structure of emerimicin-(1-9) benzyl ester (Ac-Phe-Aib-Aib-Aib-Val-Gly-Leu-Aib-Aib-OBzl) reported here shows essentially pure alpha-helical character, whereas other similar compounds show predominantly 3(10)-helical structures. The factors that govern helical preference include the inherent relative stability of the alpha-helix compared with the 3(10)-helix, the extra hydrogen bond seen with 3(10)-helices, and the enhanced electrostatic dipolar interaction of the 3(10)-helix when packed in a crystalline lattice. The balance of these forces, when combined with the steric requirements of the amino acid side chains, determines the relative stability of the two helical conformations under a given set of experimental conditions.

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Selected References

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  1. Barlow D. J., Thornton J. M. Helix geometry in proteins. J Mol Biol. 1988 Jun 5;201(3):601–619. doi: 10.1016/0022-2836(88)90641-9. [DOI] [PubMed] [Google Scholar]
  2. Bavoso A., Benedetti E., Di Blasio B., Pavone V., Pedone C., Toniolo C., Bonora G. M., Formaggio F., Crisman M. Long, chiral polypeptide 3(10)-helices at atomic resolution. J Biomol Struct Dyn. 1988 Feb;5(4):803–817. doi: 10.1080/07391102.1988.10506428. [DOI] [PubMed] [Google Scholar]
  3. Bavoso A., Benedetti E., Di Blasio B., Pavone V., Pedone C., Toniolo C., Bonora G. M. Long polypeptide 3(10)-helices at atomic resolution. Proc Natl Acad Sci U S A. 1986 Apr;83(7):1988–1992. doi: 10.1073/pnas.83.7.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burgess A. W., Leach S. J. An obligatory alpha-helical amino acid residue. Biopolymers. 1973 Nov;12(11):2599–2605. doi: 10.1002/bip.1973.360121112. [DOI] [PubMed] [Google Scholar]
  5. Esposito G., Carver J. A., Boyd J., Campbell I. D. High-resolution 1H NMR study of the solution structure of alamethicin. Biochemistry. 1987 Feb 24;26(4):1043–1050. doi: 10.1021/bi00378a010. [DOI] [PubMed] [Google Scholar]
  6. Fox R. O., Jr, Richards F. M. A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-A resolution. Nature. 1982 Nov 25;300(5890):325–330. doi: 10.1038/300325a0. [DOI] [PubMed] [Google Scholar]
  7. Furois-Corbin S., Pullman A. Theoretical study of the packing of alpha-helices into possible transmembrane bundles. Sequences including alanines, leucines and serines. Biochim Biophys Acta. 1987 Aug 7;902(1):31–45. doi: 10.1016/0005-2736(87)90133-7. [DOI] [PubMed] [Google Scholar]
  8. Hall J. E., Vodyanoy I., Balasubramanian T. M., Marshall G. R. Alamethicin. A rich model for channel behavior. Biophys J. 1984 Jan;45(1):233–247. doi: 10.1016/S0006-3495(84)84151-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Iijima H., Dunbar J. B., Jr, Marshall G. R. Calibration of effective van der Waals atomic contact radii for proteins and peptides. Proteins. 1987;2(4):330–339. doi: 10.1002/prot.340020408. [DOI] [PubMed] [Google Scholar]
  10. Karle I. L. Conformational characteristics of peptides and unanticipated results from crystal structure analyses. Biopolymers. 1989 Jan;28(1):1–14. doi: 10.1002/bip.360280104. [DOI] [PubMed] [Google Scholar]
  11. Karle I. L., Flippen-Anderson J. L., Sukumar M., Balaram P. Monoclinic polymorph of Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe(anhydrous). Parallel packing of 3(10)-/alpha-helices and a transition of helix type. Int J Pept Protein Res. 1988 Jun;31(6):567–576. doi: 10.1111/j.1399-3011.1988.tb00915.x. [DOI] [PubMed] [Google Scholar]
  12. Karle I. L., Flippen-Anderson J. L., Uma K., Balaram H., Balaram P. Alpha-helix and mixed 3(10)/alpha-helix in cocrystallized conformers of Boc-Aib-Val-Aib-Aib-Val-Val-Val-Aib-Val-Aib-OMe. Proc Natl Acad Sci U S A. 1989 Feb;86(3):765–769. doi: 10.1073/pnas.86.3.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Karle I. L., Flippen-Anderson J. L., Uma K., Balaram P. Aggregation studies in crystals of apolar helical peptides: Boc-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe. Int J Pept Protein Res. 1988 Dec;32(6):536–543. doi: 10.1111/j.1399-3011.1988.tb01385.x. [DOI] [PubMed] [Google Scholar]
  14. Karle I. L., Flippen-Anderson J., Sukumar M., Balaram P. Conformation of a 16-residue zervamicin IIA analog peptide containing three different structural features: 3(10)-helix, alpha-helix, and beta-bend ribbon. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5087–5091. doi: 10.1073/pnas.84.15.5087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Karle I. L., Flippen-Anderson J., Uma K., Balaram P. Aqueous channels within apolar peptide aggregates: solvated helix of the alpha-aminoisobutyric acid (Aib)-containing peptide Boc-(Aib-Ala-Leu)3-Aib-OMe.2H2O.CH3OH in crystals. Proc Natl Acad Sci U S A. 1988 Jan;85(2):299–303. doi: 10.1073/pnas.85.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Karle I. L., Sukumar M., Balaram P. Parallel packing of alpha-helices in crystals of the zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe.2H2O. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9284–9288. doi: 10.1073/pnas.83.24.9284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Malcolm B. R. A 310-helix in poly(alpha-aminoisobutyric acid) Biopolymers. 1977 Nov;16(11):2591–2592. doi: 10.1002/bip.1977.360161122. [DOI] [PubMed] [Google Scholar]
  18. Marshall G. R., Bosshard H. E. Angiotensin II. Studies on the biologically active conformation. Circ Res. 1972 Sep;31(9 Suppl):143–150. [PubMed] [Google Scholar]
  19. Marshall G. R., Clark J. D., Dunbar J. B., Jr, Smith G. D., Zabrocki J., Redlinski A. S., Leplawy M. T. Conformational effects of chiral alpha,alpha-dialkyl amino acids. I. C-terminal tetrapeptides of emerimicin containing alpha-ethylalanine. Int J Pept Protein Res. 1988 Dec;32(6):544–555. doi: 10.1111/j.1399-3011.1988.tb01386.x. [DOI] [PubMed] [Google Scholar]
  20. Menestrina G., Voges K. P., Jung G., Boheim G. Voltage-dependent channel formation by rods of helical polypeptides. J Membr Biol. 1986;93(2):111–132. doi: 10.1007/BF01870804. [DOI] [PubMed] [Google Scholar]
  21. Pandey R. C., Cook J. C., Jr, Rinehart K. L., Jr Structures of the peptide antibiotics. Emerimicins III and IV 1,2. J Am Chem Soc. 1977 Jul 20;99(15):5205–5206. doi: 10.1021/ja00457a064. [DOI] [PubMed] [Google Scholar]
  22. Prasad B. V., Balaram P. The stereochemistry of peptides containing alpha-aminoisobutyric acid. CRC Crit Rev Biochem. 1984;16(4):307–348. doi: 10.3109/10409238409108718. [DOI] [PubMed] [Google Scholar]
  23. Presta L. G., Rose G. D. Helix signals in proteins. Science. 1988 Jun 17;240(4859):1632–1641. doi: 10.1126/science.2837824. [DOI] [PubMed] [Google Scholar]
  24. Presta L. G., Rose G. D. Helix signals in proteins. Science. 1988 Jun 17;240(4859):1632–1641. doi: 10.1126/science.2837824. [DOI] [PubMed] [Google Scholar]
  25. Toniolo C., Bonora G. M., Bavoso A., Benedetti E., di Blasio B., Pavone V., Pedone C. Molecular structure of peptaibol antibiotics: solution conformation and crystal structure of the octapeptide corresponding to the 2-9 sequence of emerimicins III and IV. J Biomol Struct Dyn. 1985 Dec;3(3):585–598. doi: 10.1080/07391102.1985.10508446. [DOI] [PubMed] [Google Scholar]
  26. Tosteson M. T., Auld D. S., Tosteson D. C. Voltage-gated channels formed in lipid bilayers by a positively charged segment of the Na-channel polypeptide. Proc Natl Acad Sci U S A. 1989 Jan;86(2):707–710. doi: 10.1073/pnas.86.2.707. [DOI] [PMC free article] [PubMed] [Google Scholar]

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