公开(公告)号：EP3129493A4

公开(公告)日：2018-04-25

申请号：EP15777242

申请日：2015-04-09

申请人： SCRIPPS RESEARCH INST

发明人： ROMESBERG FLOYD E ,  MALYSHEV DENIS A

IPC分类号： C12P19/34 ,  A01H1/00 ,  C07H21/04 ,  C07K14/295 ,  C07K14/405 ,  C12N15/10 ,  C12N15/70

CPC分类号： C12N15/70 ,  C07K14/295 ,  C07K14/405 ,  C12N15/8243 ,  C12P19/34

摘要： A recombinantly expressed nucleotide triphosphate transporter efficiently imports the triphosphates of unnatural nucleotides into cells, and the endogenous cellular machinery incorporates those nucleotides into cellular nucleic acids. UBPs can therefore form within the cell's nucleic acids. Moreover, neither the presence of the unnatural triphosphates nor the replication of the UBP represents a significant growth burden. The UBP is not efficiently excised by nucleic acid repair pathways, and therefore can be retained as long as the unnatural triphosphates are available in the growth medium. Thus, the resulting cell is the first organism to stably propagate an expanded genetic alphabet.

公开(公告)号：EP3041854A4

公开(公告)日：2017-05-03

申请号：EP14834827

申请日：2014-08-08

申请人： SCRIPPS RESEARCH INST

发明人： ROMESBERG FLOYD E ,  MALYSHEV DENIS A ,  LI LINGJUN ,  LAVERGNE THOMAS ,  LI ZHENGTAO

IPC分类号： C07H19/00 ,  C12N15/09

CPC分类号： C07H19/24 ,  C07H19/00 ,  C07H21/00 ,  C12P19/34 ,  C12Q1/6832 ,  C12Q2525/117

公开(公告)号：EP2616093A4

公开(公告)日：2014-02-26

申请号：EP11825668

申请日：2011-08-31

申请人： SCRIPPS RESEARCH INST

发明人： ROMESBERG FLOYD E ,  SMITH PETER A ,  ROBERTS TUCKER C

IPC分类号： A61K38/04 ,  A61K38/12

CPC分类号： C07K7/06 ,  A61K38/00 ,  A61K38/08 ,  A61K38/14 ,  A61K45/06 ,  C07K9/001

摘要： Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.