- Simplified Novel Muraymycin Analogues; using a Serine Template Strategy for Linking Key Pharmacophores
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The present status of antibiotic research requires the urgent invention of novel agents that act on multidrug-resistant bacteria. The World Health Organization has classified antibiotic-resistant bacteria into critical, high and medium priority according to the urgency of need for new antibiotics. Naturally occurring uridine-derived “nucleoside antibiotics” have shown promising activity against numerous priority resistant organisms by inhibiting the transmembrane protein MraY (translocase I), which is yet to be explored in a clinical context. The catalytic activity of MraY is an essential process for bacterial cell viability and growth including that of priority organisms. Muraymycins are one subclass of naturally occurring MraY inhibitors. Despite having potent antibiotic properties, the structural complexity of muraymycins advocates for simplified analogues as potential lead structures. Herein, we report a systematic structure-activity relationship (SAR) study of serine template-linked, simplified muraymycin-type analogues. This preliminary SAR lead study of serine template analogues successfully revealed that the complex structure of naturally occurring muraymycins could be easily simplified to afford bioactive scaffolds against resistant priority organisms. This study will pave the way for the development of novel antibacterial lead compounds based on a simplified serine template.
- Patel, Bhautikkumar,Kerr, Rachel V,Malde, Alpeshkumar K,Zunk, Matthew,Bugg, Timothy D. H.,Grant, Gary,Rudrawar, Santosh
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supporting information
p. 1429 - 1438
(2020/06/17)
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- ANTIBODY-COUPLED CYCLIC PEPTIDE TYROSINE TYROSINE COMPOUNDS AS MODULATORS OF NEUROPEPTIDE Y RECEPTORS
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The present invention comprises conjugates comprising a monoclonal antibody conjugated to a cyclic PYY peptide. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel conjugates are useful for preventing, treating or ameliorating diseases and disorders disclosed herein.
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Paragraph 0387-0388
(2018/05/17)
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- Synthesis of the repeating decapeptide unit of Mefp1 in orthogonally protected form
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Mefp1 is a protein produced by the marine mussel, Mytilus edulis, which helps the organism to adhere to surfaces in turbulent waters. To better understand the nature of the adhesion process, we sought to synthesize homogeneous oligopeptides based on the repeating decapeptide unit of the protein. The fully protected decapeptide 10 has been synthesized from appropriately protected amino acid building blocks using a fragment condensation strategy. A key feature of the strategy is the late incorporation of the synthetically valuable dihydroxyproline residue. This synthesis of the orthogonally protected repeating decapeptide unit of Mefp1 represents an important first step toward producing useful quantities of homogeneous oligopeptides related to the protein.
- Taylor, Carol M.,Weir, Claudette A.
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p. 1414 - 1421
(2007/10/03)
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