Designed beta-sheet peptides that inhibit proliferation and induce apoptosis in endothelial cells.
Identifieur interne : 003444 ( Main/Exploration ); précédent : 003443; suivant : 003445Designed beta-sheet peptides that inhibit proliferation and induce apoptosis in endothelial cells.
Auteurs : K H Mayo [États-Unis] ; D W Van Der Schaft ; A W GriffioenSource :
- Angiogenesis [ 0969-6970 ] ; 2001.
Descripteurs français
- KwdFr :
- Animaux, Apoptose (), Bovins, Cellules cultivées, Conception de médicament, Division cellulaire (), Données de séquences moléculaires, Endothélium vasculaire (), Endothélium vasculaire (cytologie), Facteur-4 plaquettaire (), Humains, Interleukine-8 (), Peptides (), Peptides (pharmacologie), Peptides (synthèse chimique), Peptides antimicrobiens cationiques, Protéines du sang (), Protéines membranaires, Relation structure-activité, Structure secondaire des protéines, Séquence d'acides aminés.
- MESH :
- cytologie : Endothélium vasculaire.
- pharmacologie : Peptides.
- synthèse chimique : Peptides.
- Animaux, Apoptose, Bovins, Cellules cultivées, Conception de médicament, Division cellulaire, Données de séquences moléculaires, Endothélium vasculaire, Facteur-4 plaquettaire, Humains, Interleukine-8, Peptides, Peptides antimicrobiens cationiques, Protéines du sang, Protéines membranaires, Relation structure-activité, Structure secondaire des protéines, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antimicrobial Cationic Peptides, Apoptosis (drug effects), Blood Proteins (chemistry), Cattle, Cell Division (drug effects), Cells, Cultured, Drug Design, Endothelium, Vascular (cytology), Endothelium, Vascular (drug effects), Humans, Interleukin-8 (chemistry), Membrane Proteins, Molecular Sequence Data, Peptides (chemical synthesis), Peptides (chemistry), Peptides (pharmacology), Platelet Factor 4 (chemistry), Protein Structure, Secondary, Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Peptides.
- chemical , chemistry : Blood Proteins, Interleukin-8, Peptides, Platelet Factor 4.
- chemical , pharmacology : Peptides.
- chemical : Antimicrobial Cationic Peptides, Membrane Proteins.
- cytology : Endothelium, Vascular.
- drug effects : Apoptosis, Cell Division, Endothelium, Vascular.
- Amino Acid Sequence, Animals, Cattle, Cells, Cultured, Drug Design, Humans, Molecular Sequence Data, Protein Structure, Secondary, Structure-Activity Relationship.
Abstract
Novel beta-sheet-forming peptide 33 mers, beta pep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences or proposed key residues from the beta-sheet domains of interleukin-8 (IL-8), platelet factor-4 (PF4) and bactericidal/permeability increasing protein (B/PI). Since PF4 and B/PI are anti-angiogenic and IL-8 is angiogenic, the library of 30 beta pep peptides was assayed for the ability to affect the growth of endothelial cells. Results indicate that five beta pep peptides (beta pep-2, 7, 8, 21 and 25) demonstrate greater than 50% anti-proliferative activity at 30 micrograms/ml, and one of those (beta pep-25) is similarly active at 10 micrograms/ml. Insight into the mechanism of action was probed in an apoptosis assay. Anti-proliferative activity was found to be correlated with the induction of apoptosis. For example, at 100 micrograms/ml beta pep-25 induces 85% of endothelial cells to undergo apoptosis within 2 days. These effects from beta pep peptides appear to be selective for endothelial cell (EC) because normal cells (fibroblasts and leukocytes) and various tumor cells are not significantly affected at peptide concentrations used in this study. Comparison of active and inactive beta pep sequences allows structure-function relationships to be deduced. Five hydrophobic residues and two lysines appear to be crucial to activity. This research contributes to the development of novel anti-angiogenic peptides.
DOI: 10.1023/a:1016672117477
PubMed: 11824378
Affiliations:
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Le document en format XML
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uniqKey="Van Der Schaft D" first="D W" last="Van Der Schaft">D W Van Der Schaft</name></author><author><name sortKey="Griffioen, A W" sort="Griffioen, A W" uniqKey="Griffioen A" first="A W" last="Griffioen">A W Griffioen</name></author></analytic><series><title level="j">Angiogenesis</title><idno type="ISSN">0969-6970</idno><imprint><date when="2001" type="published">2001</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antimicrobial Cationic Peptides</term><term>Apoptosis (drug effects)</term><term>Blood Proteins (chemistry)</term><term>Cattle</term><term>Cell Division (drug effects)</term><term>Cells, Cultured</term><term>Drug Design</term><term>Endothelium, Vascular (cytology)</term><term>Endothelium, Vascular (drug effects)</term><term>Humans</term><term>Interleukin-8 (chemistry)</term><term>Membrane Proteins</term><term>Molecular Sequence Data</term><term>Peptides (chemical synthesis)</term><term>Peptides (chemistry)</term><term>Peptides (pharmacology)</term><term>Platelet Factor 4 (chemistry)</term><term>Protein Structure, Secondary</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Apoptose ()</term><term>Bovins</term><term>Cellules cultivées</term><term>Conception de médicament</term><term>Division cellulaire ()</term><term>Données de séquences moléculaires</term><term>Endothélium vasculaire ()</term><term>Endothélium vasculaire (cytologie)</term><term>Facteur-4 plaquettaire ()</term><term>Humains</term><term>Interleukine-8 ()</term><term>Peptides ()</term><term>Peptides (pharmacologie)</term><term>Peptides (synthèse chimique)</term><term>Peptides antimicrobiens cationiques</term><term>Protéines du sang ()</term><term>Protéines membranaires</term><term>Relation structure-activité</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Blood Proteins</term><term>Interleukin-8</term><term>Peptides</term><term>Platelet Factor 4</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Antimicrobial Cationic Peptides</term><term>Membrane Proteins</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Endothélium vasculaire</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Cell Division</term><term>Endothelium, Vascular</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Cattle</term><term>Cells, Cultured</term><term>Drug Design</term><term>Humans</term><term>Molecular Sequence Data</term><term>Protein Structure, Secondary</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Apoptose</term><term>Bovins</term><term>Cellules cultivées</term><term>Conception de médicament</term><term>Division cellulaire</term><term>Données de séquences moléculaires</term><term>Endothélium vasculaire</term><term>Facteur-4 plaquettaire</term><term>Humains</term><term>Interleukine-8</term><term>Peptides</term><term>Peptides antimicrobiens cationiques</term><term>Protéines du sang</term><term>Protéines membranaires</term><term>Relation structure-activité</term><term>Structure secondaire des protéines</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Novel beta-sheet-forming peptide 33 mers, beta pep peptides, have been designed by using a combination approach employing basic folding principles and incorporating short sequences or proposed key residues from the beta-sheet domains of interleukin-8 (IL-8), platelet factor-4 (PF4) and bactericidal/permeability increasing protein (B/PI). Since PF4 and B/PI are anti-angiogenic and IL-8 is angiogenic, the library of 30 beta pep peptides was assayed for the ability to affect the growth of endothelial cells. Results indicate that five beta pep peptides (beta pep-2, 7, 8, 21 and 25) demonstrate greater than 50% anti-proliferative activity at 30 micrograms/ml, and one of those (beta pep-25) is similarly active at 10 micrograms/ml. Insight into the mechanism of action was probed in an apoptosis assay. Anti-proliferative activity was found to be correlated with the induction of apoptosis. For example, at 100 micrograms/ml beta pep-25 induces 85% of endothelial cells to undergo apoptosis within 2 days. These effects from beta pep peptides appear to be selective for endothelial cell (EC) because normal cells (fibroblasts and leukocytes) and various tumor cells are not significantly affected at peptide concentrations used in this study. Comparison of active and inactive beta pep sequences allows structure-function relationships to be deduced. Five hydrophobic residues and two lysines appear to be crucial to activity. This research contributes to the development of novel anti-angiogenic peptides.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Minnesota</li></region></list><tree><noCountry><name sortKey="Griffioen, A W" sort="Griffioen, A W" uniqKey="Griffioen A" first="A W" last="Griffioen">A W Griffioen</name><name sortKey="Van Der Schaft, D W" sort="Van Der Schaft, D W" uniqKey="Van Der Schaft D" first="D W" last="Van Der Schaft">D W Van Der Schaft</name></noCountry><country name="États-Unis"><region name="Minnesota"><name sortKey="Mayo, K H" sort="Mayo, K H" uniqKey="Mayo K" first="K H" last="Mayo">K H Mayo</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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