A systematic methodology for proteome-wide identification of peptides inhibiting the proliferation and migration of endothelial cells.
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.
Karagiannis
Emmanouil D
ED
Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Popel
Aleksander S
AS
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
D010455:Peptides; D020543:Proteome
J Biol Chem. 1999 Aug 13;274(33):23349-57
10438512
Nat Med. 2000 Feb;6(2):196-9
10655109
Am J Physiol Cell Physiol. 2003 Jun;284(6):C1604-13
12734113
J Biol Chem. 2001 May 4;276(18):15240-8
11278365
Biochem Biophys Res Commun. 2007 Mar 9;354(2):434-9
17239819
Pharmacol Rev. 2006 Sep;58(3):621-81
16968952
Semin Cancer Biol. 2004 Jun;14(3):195-200
15246055
J Biol Chem. 1996 Jan 5;271(1):21-4
8550562
J Biol Chem. 1996 Nov 15;271(46):29461-7
8910613
Cell. 1997 Jan 24;88(2):277-85
9008168
Blood. 1999 Aug 1;94(3):984-93
10419890
Biochem Biophys Res Commun. 1995 Dec 5;217(1):326-32
8526929
Biochem Biophys Res Commun. 2001 Nov 23;289(1):264-8
11708810
J Biol Chem. 2003 Oct 17;278(42):40989-95
12900406
J Cell Biochem. 2008 Jul 1;104(4):1356-63
18307172
Cancer Res. 2005 Jun 15;65(12):5144-52
15958558
J Biol Chem. 2001 Aug 24;276(34):31959-68
11399763
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):967-72
17210921
Biochim Biophys Acta. 2005 Mar 14;1747(2):161-70
15698950
Int J Biochem Cell Biol. 2007;39(12):2314-23
17707681
Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14319-24
16973751
Trends Endocrinol Metab. 2006 Oct;17(8):301-7
16934485
J Exp Med. 1995 Dec 1;182(6):2069-77
7500052
Blood. 1999 Oct 1;94(7):2461-8
10498619
Adv Enzyme Regul. 1984;22:27-55
6382953
Nat Med. 1995 Jan;1(1):27-31
7584949
Biochem Biophys Res Commun. 2001 Nov 23;289(1):19-24
11708770
J Biol Chem. 2000 Jan 14;275(2):1209-15
10625665
J Leukoc Biol. 2000 Jul;68(1):1-8
10914483
Front Horm Res. 2006;35:64-73
16809923
Hypertension. 2002 Feb;39(2):224-8
11847188
J Cell Biol. 1997 Aug 11;138(3):707-17
9245797
J Biol Chem. 1997 Sep 5;272(36):22924-8
9278456
J Biol Chem. 2003 Feb 7;278(6):4238-49
12435733
Oncogene. 2005 May 19;24(22):3632-42
15782143
Science. 1999 Sep 17;285(5435):1926-8
10489375
Cancer Res. 2000 May 1;60(9):2520-6
10811134
Nat Rev Drug Discov. 2007 Apr;6(4):273-86
17396134
J Biol Chem. 2000 Aug 4;275(31):23745-50
10837460
J Endocrinol. 2003 Aug;178(2):169-75
12904165
J Cell Biol. 1993 Jul;122(2):497-511
7686555
Nature. 2000 Sep 14;407(6801):249-57
11001068
Blood. 2000 Jan 15;95(2):543-50
10627460
Biochem Biophys Res Commun. 2007 Jul 20;359(1):63-9
17531201
Eur J Cancer. 2006 Apr;42(6):768-78
16510280
Cancer Res. 2005 May 15;65(10):3967-79
15899784