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Title: Identification of novel short peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen with anti-angiogenic properties

Abstract

Angiogenesis, or neovascularization, is tightly controlled by positive and negative regulators, many of which reside in the extracellular matrix. We have now identified eight novel 19- to 20-residue peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen, which we have designated tetrastatins, pentastatins, and hexastatins, respectively. We have shown that these endogenous peptides suppress the proliferation and migration of HUVECs in vitro. By performing clustering analyses of the sequences using sequence similarity criteria and of the experimental results using a hierarchical algorithm, we report that the clusters identified by the experimental results coincide with the sequence-based clusters, indicating a tight relationship between peptide sequence and anti-angiogenic potency. These peptides may have potential as anti-angiogenic therapeutic agents.

Authors:
 [1];  [2]
  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States). E-mail: ekaragi1@jhmi.edu
  2. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States)
Publication Date:
OSTI Identifier:
20979827
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 354; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2006.12.231; PII: S0006-291X(06)02889-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALGORITHMS; AMINO ACID SEQUENCE; CELL PROLIFERATION; COLLAGEN; DRUGS; IN VITRO; PEPTIDES

Citation Formats

Karagiannis, Emmanouil D., and Popel, Aleksander S.. Identification of novel short peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen with anti-angiogenic properties. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2006.12.231.
Karagiannis, Emmanouil D., & Popel, Aleksander S.. Identification of novel short peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen with anti-angiogenic properties. United States. doi:10.1016/j.bbrc.2006.12.231.
Karagiannis, Emmanouil D., and Popel, Aleksander S.. Fri . "Identification of novel short peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen with anti-angiogenic properties". United States. doi:10.1016/j.bbrc.2006.12.231.
@article{osti_20979827,
title = {Identification of novel short peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen with anti-angiogenic properties},
author = {Karagiannis, Emmanouil D. and Popel, Aleksander S.},
abstractNote = {Angiogenesis, or neovascularization, is tightly controlled by positive and negative regulators, many of which reside in the extracellular matrix. We have now identified eight novel 19- to 20-residue peptides derived from the {alpha}4, {alpha}5, and {alpha}6 fibrils of type IV collagen, which we have designated tetrastatins, pentastatins, and hexastatins, respectively. We have shown that these endogenous peptides suppress the proliferation and migration of HUVECs in vitro. By performing clustering analyses of the sequences using sequence similarity criteria and of the experimental results using a hierarchical algorithm, we report that the clusters identified by the experimental results coincide with the sequence-based clusters, indicating a tight relationship between peptide sequence and anti-angiogenic potency. These peptides may have potential as anti-angiogenic therapeutic agents.},
doi = {10.1016/j.bbrc.2006.12.231},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 354,
place = {United States},
year = {Fri Mar 09 00:00:00 EST 2007},
month = {Fri Mar 09 00:00:00 EST 2007}
}
  • The gene encoding [alpha]6(IV) collagen, COL4A6, was identified on the human X chromosome in a head-to-head arrangement and within 452 base pairs of the [alpha]5(IV) collagen gene, COL4A5. In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes. In some families, AS cosegregates with diffuse leiomyomatosis (DL), a benign smooth muscle tumor diathesis. Here it is shown that patients with AS-DL harbor deletions that disrupt both COL4A5 and COL4A6. Thus, type IV collagen may regulate smooth muscle differentiation and morphogenesis.
  • Thrombospondin 1, the prototypical protein of the thrombospondin protein family, is a potent endogenous inhibitor of angiogenesis. Although the effects of the thrombospondin 1 on neovascularization have been well studied, little is known about the anti-angiogenic potency of other proteins or peptide fragments derived from the proteins in this family. Here we identify a set of 18 novel, anti-angiogenic 17- to 20-amino acid peptides that are derived from proteins containing type I thrombospondin motifs. We have named these peptides adamtsostatin-4, adamtsostatin-16, adamtsostatin-18, cartilostatin-1, cartilostatin-2, fibulostatin-6.2, fibulostatin-6.3, papilostatin-1, papilostatin-2, properdistatin, scospondistatin, semastatin-5A.1, semastatin-5A.2, semastatin-5B, thrombostatin containing-1, thrombostatin contaning-3, thrombostatin contaning-6, andmore » wispostatin-1 to reflect their origin. We further demonstrate that these peptides inhibit the proliferation and migration of human umbilical vein endothelial cells in vitro. The anti-proliferative and anti-migratory properties of the identified peptides may be important in maintaining angiogenic homeostasis in vivo and make these peptides suitable candidates for use as anti-angiogenic pharmaceutical agents in numerous therapeutic applications.« less
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