title: A systematic methodology for proteome-wide identification of peptides inhibiting the proliferation and migration of endothelial cells.
abstract: We introduce a systematic computational methodology based on bioinformatics that has enabled us to identify and classify >120 endogenous peptide inhibitors of endothelial cell proliferation and migration. These peptides are derived from members of the type IV collagen, thrombospondin, and CXC chemokine protein families, as well as somatotropin hormones, serpins, and various kringle-containing proteins. Their activity in suppressing the proliferation and migration of endothelial cells in vitro provides proof of principle for the validity of this computational method. Interestingly, some of the peptides are derived from proteins known to be proangiogenic. By performing receptor neutralization studies, we have identified receptors to which these peptides bind. On the basis of this receptor-binding information, we evaluated several examples of peptide-based combinatorial screening strategies. In some cases, this combinatorial screening identified strong synergism between peptides. The current work provides a guideline for a computational-based peptidomics approach for the discovery of endogenous bioactive peptides.
authors.affiliation: Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Emmanouil D
authors.initials: ED
authors.lastname: Karagiannis
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D019295:Computational Biology; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis* / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010802:Phylogeny; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D010455:Peptides; D020543:Proteome
references.citation: J Biol Chem. 1999 Aug 13;274(33):23349-57
references.pmid: 10438512
references.citation: Nat Med. 2000 Feb;6(2):196-9
references.pmid: 10655109
references.citation: Am J Physiol Cell Physiol. 2003 Jun;284(6):C1604-13
references.pmid: 12734113
references.citation: J Biol Chem. 2001 May 4;276(18):15240-8
references.pmid: 11278365
references.citation: Biochem Biophys Res Commun. 2007 Mar 9;354(2):434-9
references.pmid: 17239819
references.citation: Pharmacol Rev. 2006 Sep;58(3):621-81
references.pmid: 16968952
references.citation: Semin Cancer Biol. 2004 Jun;14(3):195-200
references.pmid: 15246055
references.citation: J Biol Chem. 1996 Jan 5;271(1):21-4
references.pmid: 8550562
references.citation: J Biol Chem. 1996 Nov 15;271(46):29461-7
references.pmid: 8910613
references.citation: Cell. 1997 Jan 24;88(2):277-85
references.pmid: 9008168
references.citation: Blood. 1999 Aug 1;94(3):984-93
references.pmid: 10419890
references.citation: Biochem Biophys Res Commun. 1995 Dec 5;217(1):326-32
references.pmid: 8526929
references.citation: Biochem Biophys Res Commun. 2001 Nov 23;289(1):264-8
references.pmid: 11708810
references.citation: J Biol Chem. 2003 Oct 17;278(42):40989-95
references.pmid: 12900406
references.citation: J Cell Biochem. 2008 Jul 1;104(4):1356-63
references.pmid: 18307172
references.citation: Cancer Res. 2005 Jun 15;65(12):5144-52
references.pmid: 15958558
references.citation: J Biol Chem. 2001 Aug 24;276(34):31959-68
references.pmid: 11399763
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):967-72
references.pmid: 17210921
references.citation: Biochim Biophys Acta. 2005 Mar 14;1747(2):161-70
references.pmid: 15698950
references.citation: Int J Biochem Cell Biol. 2007;39(12):2314-23
references.pmid: 17707681
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14319-24
references.pmid: 16973751
references.citation: Trends Endocrinol Metab. 2006 Oct;17(8):301-7
references.pmid: 16934485
references.citation: J Exp Med. 1995 Dec 1;182(6):2069-77
references.pmid: 7500052
references.citation: Blood. 1999 Oct 1;94(7):2461-8
references.pmid: 10498619
references.citation: Adv Enzyme Regul. 1984;22:27-55
references.pmid: 6382953
references.citation: Nat Med. 1995 Jan;1(1):27-31
references.pmid: 7584949
references.citation: Biochem Biophys Res Commun. 2001 Nov 23;289(1):19-24
references.pmid: 11708770
references.citation: J Biol Chem. 2000 Jan 14;275(2):1209-15
references.pmid: 10625665
references.citation: J Leukoc Biol. 2000 Jul;68(1):1-8
references.pmid: 10914483
references.citation: Front Horm Res. 2006;35:64-73
references.pmid: 16809923
references.citation: Hypertension. 2002 Feb;39(2):224-8
references.pmid: 11847188
references.citation: J Cell Biol. 1997 Aug 11;138(3):707-17
references.pmid: 9245797
references.citation: J Biol Chem. 1997 Sep 5;272(36):22924-8
references.pmid: 9278456
references.citation: J Biol Chem. 2003 Feb 7;278(6):4238-49
references.pmid: 12435733
references.citation: Oncogene. 2005 May 19;24(22):3632-42
references.pmid: 15782143
references.citation: Science. 1999 Sep 17;285(5435):1926-8
references.pmid: 10489375
references.citation: Cancer Res. 2000 May 1;60(9):2520-6
references.pmid: 10811134
references.citation: Nat Rev Drug Discov. 2007 Apr;6(4):273-86
references.pmid: 17396134
references.citation: J Biol Chem. 2000 Aug 4;275(31):23745-50
references.pmid: 10837460
references.citation: J Endocrinol. 2003 Aug;178(2):169-75
references.pmid: 12904165
references.citation: J Cell Biol. 1993 Jul;122(2):497-511
references.pmid: 7686555
references.citation: Nature. 2000 Sep 14;407(6801):249-57
references.pmid: 11001068
references.citation: Blood. 2000 Jan 15;95(2):543-50
references.pmid: 10627460
references.citation: Biochem Biophys Res Commun. 2007 Jul 20;359(1):63-9
references.pmid: 17531201
references.citation: Eur J Cancer. 2006 Apr;42(6):768-78
references.pmid: 16510280
references.citation: Cancer Res. 2005 May 15;65(10):3967-79
references.pmid: 15899784