Compositions and methods for inhibiting hepatocyte invasion by malarial sporozoites
AssigneeNew York University
InventorsCarla Cerami, Ute Frevert, Photini Sinnis, Victor Nussenzweig
Life of this patent
Estimating the term…
Abstract
There is provided peptide and mimetic inhibitors for the binding of a circumsporozoite polypeptide to receptors of hepatocytes from malaria-susceptible mammals. Also contemplated is a method of inhibiting the binding of a malaria sporozoites to hepatocytes susceptible to sporozoite invasion. A peptide of Region II+ of the circumsporozoite protein is also provided, as is a method of targeting the delivery of substances to hepatocytes.
Claims46
A peptide inhibitor for the binding of a circumsporozoite polypeptide to receptors of hepatocytes from malaria-susceptible mammals, said inhibitor having an amino acid sequence selected from the group consisting of:
- (i) Region II+ of a circumsporozoite protein, said Region II+ containing the subsequence CSVTCG;
- (ii) fragments of said Region II+ containing at least a portion of the adhesion ligand for said receptors, said portion comprising at least one cysteine of said Region II+;
- (iii) peptide constructs comprising (a) (i) or (ii) and (b) at least one other fragment of the amino acid sequence of said circumsporozoite protein, said constructs having no substantial ability to elicit the formation of antibodies recognizing the immunodominant epitope of said circumsporozoite protein.
A peptide inhibitor for the binding of a circumsporozoite polypeptide to basolateral plasma membrane of hepatocytes from malaria-susceptible mammals, said inhibitor having an amino acid sequence selected from the group consisting of:
- (i) Region II+ of a circumsporozoite protein, said Region II+ containing the subsequence CSVTCG;
- (ii) fragments of said Region II+ containing at least a portion of the adhesion ligand for said receptors, said portion comprising at least one cysteine of said Region II;
- (iii) peptide constructs comprising (a) (i) or (ii) and (b) at least one other fragment of the amino acid sequence of said circumsporozoite protein, said constructs having no substantial ability to elicit the formation of antibodies recognizing the immunodominant epitope of said circumsporozoite protein.
A peptide consisting essentially of Region II+ of the circumsporozoite protein.
The method of claim 22, wherein said hepatocytes are human hepatocytes.
Dependencies are inferred from the claim text.