title: Blocking peptides and molecular mimicry as treatment for kidney disease.
abstract: Protein mimotopes, or blocking peptides, are small therapeutic peptides that prevent protein-protein interactions by selectively mimicking a native binding domain. Inexpensive technology facilitates straightforward design and production of blocking peptides in sufficient quantities to allow preventive and therapeutic trials in both in vitro and in vivo experimental disease models. The kidney is an ideal peptide target, since small molecules undergo rapid filtration and efficient bulk absorption by tubular epithelial cells. Because the half-life of peptides is markedly prolonged in the kidneys compared with the bloodstream, blocking peptides are an attractive tool for treating diverse renal diseases, including ischemia, proteinuric states, such as membranous nephropathy and focal and segmental glomerulosclerosis, and renal cell carcinoma. Therapeutic peptides represent one of the fastest-growing reagent classes for novel drug development in human disease, partly because of their ease of administration, high binding affinity, and minimal off-target effects. This review introduces the concepts of blocking peptide design, production, and administration and highlights the potential use of therapeutic peptides to prevent or treat specific renal diseases.
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Andrea
authors.initials: A
authors.lastname: Havasi
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Weining
authors.initials: W
authors.lastname: Lu
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Herbert T
authors.initials: HT
authors.lastname: Cohen
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Laurence
authors.initials: L
authors.lastname: Beck
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Chinaemare
authors.initials: C
authors.lastname: Igwebuike
authors.affiliation: Renal Section, Boston University Medical Center, Boston, Massachusetts sborkan@bu.edu.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Borkan
mesh_terms: D000818:Animals; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018716:Molecular Mimicry; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction / Q000187:drug effects; D064804:Urological Agents / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D064804:Urological Agents
keywords: Bax; Jade-1; acute kidney injury; foot process; ischemia; membranous nephropathy; nucleophosmin; phospholipase A2 receptor; podocyte; renal cell carcinoma; slit diaphragm