Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• gramicidin S synthetase GrsB [44]. Combined with the peptidyl carrier protein, GrsB PCP-TE was tested by using corresponding pentapeptides NAC thioester and thiophenol thioester, which led to the formation of the desired cyclic decapeptide lactam gramicidin S (9) through a sequential dimerization and

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• investigated the influence of a modification of 2′-OH in the AMS scaffold with different functional groups on binding to target enzymes and bacterial cell penetration. The inhibitor 7 with a cyanomethyl group at 2′-OH showed desirable inhibitory activity against both recombinant and intracellular gramicidin S

• synthetase A (GrsA) in the gramicidin S-producer Aneurinibacillus migulanus ATCC 9999, providing an alternative scaffold to develop novel A-domain inhibitors. Keywords: adenylation domain inhibitor; gramicidin S synthetase; natural product; nonribosomal peptide; nonribosomal peptide synthetase

• introduced a pegylated biotin linker at the 2′-OH group of ʟ-Phe-AMS and confirmed that the probe retains the binding activities toward the A-domain of GrsA, a gramicidin S synthetase. Aldrich et al. developed a Sal-AMS-based activity-based probe (ABP) to profile MbtA in M. tuberculosis [12]. In contrast, we

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism Danio

• , (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure–toxicity relationship data, and (v) select promising candidates for potential clinical development. Keywords: diarylethene photoswitch; gramicidin S

• photoswitch into the backbone of gramicidin S (1, GS), which is an intrinsically biostable cyclic peptide, as exemplified by one of our first prototypes compound 2 (Figure 1C). This natural antimicrobial agent has an amphipathic structure, whose functional mechanism is attributed to the permeabilization of

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• activities of the synAMPs (MIC values) were compared to those of GS(K2Y2) (Y = D-tyrosine), a gramicidin S analogue, and vancomycin, one of the last lines of defense against Staphylococcus infections. From the antibacterial activity screening, the two most active peptides were selected for further analysis

• activities of these RW-based synAMPs and their organometallic conjugates into perspective, two reference peptides were included, i.e., membrane-targeting gramicidin S derivative GS(K2Y2) and cell wall precursor lipid II-targeting vancomycin. For the calculations of the MIC values in µM, molecular weights of

• of the synAMPs against Gram-positive bacteria are only slightly lower than those of gramicidin S derivative GS(K2Y2), a peptide that contains twice as many amino acids as RcCO-W(RW)2. Interestingly, the replacement of the acetyl-group in Ac(RW)3 with the ferrocenoyl moiety results in more active

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• ; Introduction Diverse cyclic peptides, both natural and synthesized, are potent antibiotics [1][2][3]. Gramicidin S, vancomycine, bacitracin, polymixin B, colistin, valinomycin, actinomycin, and many more, have been tested and used clinically as antimicrobial and antifungal agents: It is believed that cyclic