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Complete synthesis of the bicyclic ring of a mutacin analog with orthogonally protected lanthionine via solid‐phase intracyclization
Author(s) -
Kirichenko Kostyantyn,
Hillman Jeffrey D.,
Handfield Martin,
Park Jae H.
Publication year - 2019
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3214
Subject(s) - lanthionine , lantibiotics , bicyclic molecule , peptide , chemistry , combinatorial chemistry , stereochemistry , ring (chemistry) , peptide synthesis , nisin , cysteine , biochemistry , organic chemistry , antimicrobial , enzyme
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.