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. 2017 Nov 9;9(2):350-355.
doi: 10.1039/c7sc03553e. eCollection 2018 Jan 14.

Epimerization-free access to C-terminal cysteine peptide acids, carboxamides, secondary amides, and esters via complimentary strategies

Christine A Arbour  1 , Thilini D Kondasinghe  1 , Hasina Y Saraha  1 , Teanna L Vorlicek  1 , Jennifer L Stockdill  1
Affiliations

Epimerization-free access to C-terminal cysteine peptide acids, carboxamides, secondary amides, and esters via complimentary strategies

Christine A Arbour et al. Chem Sci. .

Abstract

C-Terminal cysteine peptide acids are difficult to access without epimerization of the cysteine α-stereocenter. Diversification of the C-terminus after solid-phase peptide synthesis poses an even greater challenge because of the proclivity of the cysteine α-stereocenter to undergo deprotonation upon activation of the C-terminal carboxylic acid. We present herein two general strategies to access C-terminal cysteine peptide derivatives without detectable epimerization, diketopiperazine formation, or piperidinylalanine side products.

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Figures

Scheme 1
Scheme 1. Our strategy for C-terminal functionalization of non-Cys terminated peptides.
Scheme 2
Scheme 2. Synthesis of conotoxin α-ImI (10).
Scheme 3
Scheme 3. Synthesis of α-factor by cysteine elongation.
See this image and copyright information in PMC

References

    1. Clarke S. Annu. Rev. Biochem. 1992;61:355–386. - PubMed
    2. Glomset J. A., Gelb M. H., Farnsworth C. C. Trends Biochem. Sci. 1990;15:139–142. - PubMed
    3. Hrycyna C. A., Clarke S. Mol. Cell. Biol. 1990;10:5071–5076. - PMC - PubMed
    4. Zhang F. L., Casey P. J. Annu. Rev. Biochem. 1992;65:241–269. - PubMed
    5. Mullen D. G., Kyro K., Hauser M., Gustavsson M., Veglia G., Becker J. M., Naider F., Distefano M. D. Bioorg. Med. Chem. 2011;19:490–497. - PMC - PubMed
    6. Diaz-Rodriguez V., Mullen D. G., Ganusova E., Becker J. M., Distefano M. D. Org. Lett. 2012;14:5648–5651. - PMC - PubMed
    7. Diaz-Rodriguez V., Ganusova E., Rappe T. M., Becker J. M., Distefano M. D. J. Org. Chem. 2015;80:11266–11274. - PMC - PubMed
    8. Naider F. R., Becker J. M. Pept. Sci.: Present Future, Proc. Int. Pept. Symp., 1st. 1997:3–14.
    1. Craik D. J., Adams D. J. ACS Chem. Biol. 2007;2:457–468. - PubMed
    2. Inserra M. C., Kompella S. N., Vetter S. N., Brust A., Daly N. L., Cuny H., Craik D. J., Alewood P. F., Adams D. J., Lewis R. J. Biochem. Pharmacol. 2013;86:791–799. - PubMed
    3. Gould A., Camarero J. A. ChemBioChem. 2017;18:1350–1363. - PMC - PubMed
    1. Shang W., Yang X., Ju X., Xie Y., Zhang Y., Lee W.-H. J. Pept. Sci. 2017;23:707–715. - PubMed
    1. Conlon J. M., Musale V., Attoub S., Mangoni M. L., Leprince J., Coquet L., Jouenne T., Abdel-Wahab Y. H. A., Flatt P. R., Rinaldi A. C. J. Pept. Sci. 2017;23:769–776. - PubMed
    1. Kang T. S., Vivekanandan S., Jois S. D. S., Kini R. M. Angew. Chem., Int. Ed. 2005;44:6333–6337. - PubMed