Ipglycermides

Ipglycermide Ce-2 Y7F
Chemical and physical data
FormulaC82H102N16O25S2
Molar mass1775.93 g·mol−1
3D model (JSmol)
  • O=C(NC(CC1=CC=C(O)C=C1)C(NC(CC(C)C)C(NC(CC2=CC=C(O)C=C2)C(NCC(NC(C(O)C)C(NC(CS)C(NCC(N)=O)=O)=O)=O)=O)=O)=O)[C@@H]3CSCC(N[C@H](CC4=CC=C(O)C=C4)C(NC(CC(O)=O)C(N[C@H](CC5=CC=C(O)C=C5)C(N6C(CCC6)C(NCC(N[C@@H](CC(O)=O)C(N[C@@H](CC7=CC=CC=C7)C(N3)=O)=O)=O)=O)=O)=O)=O)=O
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Ipglycermide Sa-D3
Chemical and physical data
FormulaC87H111N19O23S
Molar mass1823.02 g·mol−1
3D model (JSmol)
  • OC(CC[C@H](NC([C@H](CC1=CNC2=C1C=CC=C2)NC([C@@H]3CCCN3C([C@H](CO)N(C)C([C@@H](NC([C@H](CC4=CNC5=C4C=CC=C5)NC([C@H](CC6=CNC7=C6C=CC=C7)NC([C@H](C(C)C)NC([C@]([H])([C@@H](C)O)NC([C@H](C(C)C)NC([C@H](CCC(N)=O)NC([C@@H](CC8=CC=C(O)C=C8)NC9=O)=O)=O)=O)=O)=O)=O)=O)C)=O)=O)=O)=O)C(N[C@@H](CC(O)=O)C(N[C@@H](CSC9)C(N)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.


Ipglycermide Ce-2
Chemical and physical data
FormulaC82H102N16O26S2
Molar mass1791.92 g·mol−1
3D model (JSmol)
  • O=C(NC(CC1=CC=C(O)C=C1)C(NC(CC(C)C)C(NC(CC2=CC=C(O)C=C2)C(NCC(NC(C(O)C)C(NC(CS)C(NCC(N)=O)=O)=O)=O)=O)=O)=O)[C@@H]3CSCC(N[C@H](CC4=CC=C(O)C=C4)C(NC(CC(O)=O)C(N[C@H](CC5=CC=C(O)C=C5)C(N6C(CCC6)C(NCC(N[C@@H](CC(O)=O)C(N[C@@H](CC7=CC=C(O)C=C7)C(N3)=O)=O)=O)=O)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.


Ipglycermide Ce-2d
Chemical and physical data
FormulaC71H84N12O21S
Molar mass1473.58 g·mol−1
3D model (JSmol)
  • O=C(NC(CC1=CC=C(O)C=C1)C(NC(CC(C)C)C(NC(CC2=CC=C(O)C=C2)C(N)=O)=O)=O)[C@@H]3CSCC(N[C@H](CC4=CC=C(O)C=C4)C(NC(CC(O)=O)C(N[C@H](CC5=CC=C(O)C=C5)C(N6C(CCC6)C(NCC(N[C@@H](CC(O)=O)C(N[C@@H](CC7=CC=C(O)C=C7)C(N3)=O)=O)=O)=O)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.


Ipglycermide Ce-1 NHOH
Chemical and physical data
FormulaC74H92N16O24S
Molar mass1621.70 g·mol−1
3D model (JSmol)
  • O=C(NC(CC1=CC=C(O)C=C1)C(NC(CC(C)C)C(NC(CC2=CC=C(O)C=C2)C(NCC(NC(C(O)C)C(NO)=O)=O)=O)=O)=O)[C@@H]3CSCC(N[C@H](CC4=CC=C(O)C=C4)C(NC(CC(O)=O)C(N[C@H](CC5=CC=C(O)C=C5)C(N6C(CCC6)C(NCC(N[C@@H](CC(O)=O)C(N[C@@H](CC7=CNC=N7)C(N3)=O)=O)=O)=O)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.


Ipglycermide Sa-D2
Chemical and physical data
FormulaC88H119N19O23S2
Molar mass1875.15 g·mol−1
3D model (JSmol)
  • O=C(NC(CC1=CC=C(O)C=C1)C(NC(CC(C)C)C(NC(CC2=CC=C(O)C=C2)C(N)=O)=O)=O)[C@@H]3CSCC(N[C@H](CC4=CC=C(O)C=C4)C(NC(CC(O)=O)C(N[C@H](CC5=CC=C(O)C=C5)C(N6C(CCC6)C(NCC(N[C@@H](CC(O)=O)C(N[C@@H](CC7=CC=C(O)C=C7)C(N3)=O)=O)=O)=O)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.
Ipglycermide Ce-2d
Chemical and physical data
FormulaC71H84N12O21S
Molar mass1473.58 g·mol−1
3D model (JSmol)
  • OC(CC[C@H](NC([C@H](CC1=CNC2=C1C=CC=C2)NC([C@@H]3CCCN3C([C@H](CO)N(C)C([C@@H](NC([C@H](CC4=CNC5=C4C=CC=C5)NC([C@H](CC6=CNC7=C6C=CC=C7)NC([C@H](C(C)C)NC([C@]([H])([C@@H](C)O)NC([C@H](C(C)C)NC([C@H](CCC(N)=O)NC([C@@H](CC8=CC=C(O)C=C8)NC9=O)=O)=O)=O)=O)=O)=O)=O)C)=O)=O)=O)=O)C(N[C@@H](CC(O)=O)C(N[C@@H](CSC9)C(N)=O)=O)=O)=O
Error in template * unknown parameter name (Template:Infobox_drug): "1; 2" (See parameter list). This message only shows in Preview, it will not show after you do Publish changes.

Ipglycermides are non-natural macrocyclic peptide (MCP) inhibitors of cofactor independent phosphoglycerate mutases (iPGM) discovered by the research laboratories of Dr. James Inglese of the National Institutes of Health and Prof. Hiroaki Suga of the University of Tokyo. It is part of a class of drugs or potential drugs composed of a loop of amino acids with a molecular weight of 700 to 2000 daltons. Thus, compared to most small-molecule drugs, there are more interactions with the drug target that allow them to work at significantly lower concentrations.

Over eons Nature has evolved numerous cyclic peptides for signaling and host defense [1]. This class of molecule has found therapeutic use as antibiotics (e.g., vancomycin, bacitracin), immunosuppressants (e.g., ciclosporin), and chemotherapeutics (e.g., romidepsin). The restricted conformations associated with cyclic peptides vs their linear counterparts bestow advantages in potency and stability. With advances in the generation of very large synthetic cyclic peptide libraries and in vitro affinity-based selection methods [2], scientists have begun to harness the potential of this molecular modality as a template for novel ligands in drug development and other applications. However, while approaches in de novo discovery of synthetic high affinity and selective cyclic peptides progressed significantly, properties including cell permeability and metabolic stability remain challenging to incorporate and represents an active area of study in the field [3]

  1. ^ Abdalla, M.A.; McGaw, L.J. (2018). "Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review". Molecules. 23 (8): 2080. doi:10.3390/molecules23082080. PMC 6222632. PMID 30127265.
  2. ^ Schlippe, Y.V.G.; Hartman, M.C.T.; Josephson, K.; Szostak, J.W. (2012). "in Vitro Selection of Highly Modified Cyclic Peptides That Act as Tight Binding Inhibitors". Journal of the American Chemical Society. 134 (25): 10469–10477. doi:10.1021/ja301017y. PMC 3384292. PMID 22428867.
  3. ^ Faris, J.H.; Adaligil, E.; Popovych, N.; Ono, S.; Takahashi, M.; Nguyen, H.; Plise, E.; Taechalertpaisarn, J.; Lee, H.W.; Koehler, M.F.T.; Cunningham, C.N.; Lokey, R.S. (2024). "Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation". J Am Chem Soc. 146 (7): 4582–91. doi:10.1021/jacs.3c10949. PMC 10885153. PMID 38330910.