Transmembrane peptidic antagonists of plexin-a1 and their therapeutic uses
AssigneesUniversite De Strasbourg, Institut National De La Sante Et De La Recherche Medicale (Inserm)
InventorsDominique BAGNARD, Fabien BINAME
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Abstract
The present application relates to peptides derived from the transmembrane domain of Plexin-A1 that inhibits Neu-ropilin-1/Plexin-A1 heterodimerization. These peptides neutralize the inhibitory effect of Sema3A on cell migration and angiogenesis, and may be useful for the treatment of diseases associated with Sema3A and/or Neuropilin-1/Plexin-A1 activity, such as demyelinating diseases and diseases associated with abnormal angiogenesis such as cancer.
Claims22
1-68. (canceled)
A peptide comprising:
- a first domain of the sequence X37-X5-X6-X7-G, and
- (i) a second domain of the formula I:
- -(X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36)-(CterpolyD/E) directly linked at carboxy-terminal end of the first domain;
- (ii) a second domain of the formula II:
- -(X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23-X24-X25)-(CterGp) directly linked at carboxy-terminal end of the first domain;
- or
- (iii) a second domain of the formula III:
- (NterGp)-(X8-X9-X10-X11-X12)-directly linked at amino-terminal end of the first domain;
- wherein
- X37 is Gly, L-Ser or D-Ser;
- X5, X6 and X7 are independently any amino acid;
- X8, X9, X10, X11 and X12 are independently any amino acid,
- X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24 and X25 are independently any amino acid, wherein no more than 2 amino acids among X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24 and X25 are a charged amino acid;
- X26, X27, X28, X29, X30, X31, X32, X33, X34, X35 and X36 are independently any amino acid, wherein no more than 2 amino acids among X26, X27, X28, X29, X30, X31, X32, X33, X34, X35 are a charged amino acid;
- CterpolyD/E is a group of 4-10 amino acids including at least 2 negatively charged amino acids;
- NterGp is a group of 3-5 amino acids including at least 2 charged amino acids, and
- CterGp is a group of 3-5 amino acids including at least 3 positively charged amino acids,
- or a retro or retroinverso form thereof,
- or a pharmaceutically acceptable salt thereof.
A method for treating a demyelinating disease in a subject in need thereof, the method comprising administering to the subject an effective amount of the peptide, retro or retroinverso form thereof, or pharmaceutically acceptable salt thereof according to claim 68, or a pharmaceutical composition comprising the peptide, retro or retroinverso form thereof, or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.