Complete synthesis of the bicyclic ring of a mutacin analog with orthogonally protected lanthionine via solid-phase intracyclization.

Autor: Kirichenko K; Oragenics, Department of Research and Development, Oragenics, Inc., Alachua, Florida, U.S.A.; SynQuest Laboratories, Inc., Alachua, Florida, U.S.A., Hillman JD; Oragenics, Department of Research and Development, Oragenics, Inc., Alachua, Florida, U.S.A., Handfield M; Oragenics, Department of Research and Development, Oragenics, Inc., Alachua, Florida, U.S.A., Park JH; Oragenics, Department of Research and Development, Oragenics, Inc., Alachua, Florida, U.S.A.
Jazyk: angličtina
Zdroj: Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2019 Nov; Vol. 25 (11), pp. e3214.
DOI: 10.1002/psc.3214
Abstrakt: Mutacin 1140 (MU1140) is a naturally occurring lantibiotic derived from posttranslational modifications of a ribosomally synthesized peptide during the fermentation of a bacterium called Streptococcus mutans, the etiological agent of dental cavities. A practical approach for chemically synthesizing lantibiotics would be a valuable tool to expand the MU1140 library with additional semisynthetic analogs. In turn, an expanded library may prove useful to explore additional therapeutic indications for this pipeline of novel compounds. In this work, orthogonally protected lanthionine analogs were synthesized via an aziridine ring opening strategy. This lanthionine was utilized to synthesize a cysteamine (Cya) instead of the (S)-aminovinyl-D-cysteine (AviCys) that is naturally found in MU1140. The Cya containing bicyclic C/D ring of MU1140 was synthesized by Fmoc solid-phase peptide synthesis (SPPS). The linear peptides were synthesized using OPfp ester derivatives and using various common coupling reagents such as COMU and TCTU. The linear peptide was intracyclized with DEPBT to construct the so-called bicyclic ring C/D. This is the first report on the complete chemical synthesis of the bicyclic C/D ring of a MU1140 analog using orthogonally protected lanthionines using SPPS.
(© 2019 European Peptide Society and John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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