In vitro inhibition of Ras-Raf association by short peptides.
Identifieur interne : 003997 ( Main/Exploration ); précédent : 003996; suivant : 003998In vitro inhibition of Ras-Raf association by short peptides.
Auteurs : D. Barnard [États-Unis] ; H. Sun ; L. Baker ; M S MarshallSource :
- Biochemical and biophysical research communications [ 0006-291X ] ; 1998.
Descripteurs français
- KwdFr :
- Données de séquences moléculaires, Fragments peptidiques (métabolisme), Fragments peptidiques (pharmacologie), Humains, Liaison aux protéines (), Oligopeptides (génétique), Oligopeptides (pharmacologie), Oligopeptides (synthèse chimique), Protéines G ras (antagonistes et inhibiteurs), Protéines G ras (métabolisme), Protéines proto-oncogènes c-raf (), Protéines proto-oncogènes c-raf (antagonistes et inhibiteurs), Protéines proto-oncogènes c-raf (métabolisme), Relation structure-activité, Sites de fixation (), Substitution d'acide aminé, Séquence d'acides aminés.
- MESH :
- antagonistes et inhibiteurs : Protéines G ras, Protéines proto-oncogènes c-raf.
- génétique : Oligopeptides.
- métabolisme : Fragments peptidiques, Protéines G ras, Protéines proto-oncogènes c-raf.
- pharmacologie : Fragments peptidiques, Oligopeptides.
- synthèse chimique : Oligopeptides.
- Données de séquences moléculaires, Humains, Liaison aux protéines, Protéines proto-oncogènes c-raf, Relation structure-activité, Sites de fixation, Substitution d'acide aminé, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Amino Acid Substitution, Binding Sites (drug effects), Humans, Molecular Sequence Data, Oligopeptides (chemical synthesis), Oligopeptides (genetics), Oligopeptides (pharmacology), Peptide Fragments (metabolism), Peptide Fragments (pharmacology), Protein Binding (drug effects), Proto-Oncogene Proteins c-raf (antagonists & inhibitors), Proto-Oncogene Proteins c-raf (chemistry), Proto-Oncogene Proteins c-raf (metabolism), Structure-Activity Relationship, ras Proteins (antagonists & inhibitors), ras Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Proto-Oncogene Proteins c-raf, ras Proteins.
- chemical , chemical synthesis : Oligopeptides.
- chemical , chemistry : Proto-Oncogene Proteins c-raf.
- drug effects : Binding Sites, Protein Binding.
- chemical , genetics : Oligopeptides.
- chemical , metabolism : Peptide Fragments, Proto-Oncogene Proteins c-raf, ras Proteins.
- chemical , pharmacology : Oligopeptides, Peptide Fragments.
- Amino Acid Sequence, Amino Acid Substitution, Humans, Molecular Sequence Data, Structure-Activity Relationship.
Abstract
Seven amino acid peptides were tested as in vitro inhibitors of oncogenic Ras-Raf association. The sequences of these peptides were derived from the H-Ras effector region (amino acids 25 to 51) and the Ras binding domain of Raf-1 (amino acids 64 to 105). Eleven out of the twenty-one Ras 7-mers tested inhibited formation of the Ras-Raf complex by at least 20% at 100 microM. The most potent of these inhibitory peptides contained the effector residues 32 to 37 or 40 to 45. Of the Raf-1 peptides tested, only the 94-ECCAVFR-100 and 95-CCAVFRL-101 peptides were significant inhibitors of Ras-Raf binding. The 95-101 Raf peptide had an IC50 value of 7 microM and also inhibited Ras-RalGDS binding. Analysis of the 95-101 peptide showed that its inhibitory activity required at least one cysteine followed by several hydrophobic residues. Our results demonstrate the feasibility of using small molecules as inhibitors of Ras protein-protein interactions.
DOI: 10.1006/bbrc.1998.8746
PubMed: 9636675
Affiliations:
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Barnard</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Indiana University School of Medicine, Indianapolis 46202</wicri:regionArea><wicri:noRegion>Indianapolis 46202</wicri:noRegion></affiliation></author><author><name sortKey="Sun, H" sort="Sun, H" uniqKey="Sun H" first="H" last="Sun">H. Sun</name></author><author><name sortKey="Baker, L" sort="Baker, L" uniqKey="Baker L" first="L" last="Baker">L. Baker</name></author><author><name sortKey="Marshall, M S" sort="Marshall, M S" uniqKey="Marshall M" first="M S" last="Marshall">M S Marshall</name></author></analytic><series><title level="j">Biochemical and biophysical research communications</title><idno type="ISSN">0006-291X</idno><imprint><date when="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Binding Sites (drug effects)</term><term>Humans</term><term>Molecular Sequence Data</term><term>Oligopeptides (chemical synthesis)</term><term>Oligopeptides (genetics)</term><term>Oligopeptides (pharmacology)</term><term>Peptide Fragments (metabolism)</term><term>Peptide Fragments (pharmacology)</term><term>Protein Binding (drug effects)</term><term>Proto-Oncogene Proteins c-raf (antagonists & inhibitors)</term><term>Proto-Oncogene Proteins c-raf (chemistry)</term><term>Proto-Oncogene Proteins c-raf (metabolism)</term><term>Structure-Activity Relationship</term><term>ras Proteins (antagonists & inhibitors)</term><term>ras Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Données de séquences moléculaires</term><term>Fragments peptidiques (métabolisme)</term><term>Fragments peptidiques (pharmacologie)</term><term>Humains</term><term>Liaison aux protéines ()</term><term>Oligopeptides (génétique)</term><term>Oligopeptides (pharmacologie)</term><term>Oligopeptides (synthèse chimique)</term><term>Protéines G ras (antagonistes et inhibiteurs)</term><term>Protéines G ras (métabolisme)</term><term>Protéines proto-oncogènes c-raf ()</term><term>Protéines proto-oncogènes c-raf (antagonistes et inhibiteurs)</term><term>Protéines proto-oncogènes c-raf (métabolisme)</term><term>Relation structure-activité</term><term>Sites de fixation ()</term><term>Substitution d'acide aminé</term><term>Séquence d'acides aminés</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Proto-Oncogene Proteins c-raf</term><term>ras Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Oligopeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Proto-Oncogene Proteins c-raf</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines G ras</term><term>Protéines proto-oncogènes c-raf</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Binding Sites</term><term>Protein Binding</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Oligopeptides</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Oligopeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptide Fragments</term><term>Proto-Oncogene Proteins c-raf</term><term>ras Proteins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Fragments peptidiques</term><term>Protéines G ras</term><term>Protéines proto-oncogènes c-raf</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Fragments peptidiques</term><term>Oligopeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Oligopeptides</term><term>Peptide Fragments</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Oligopeptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Amino Acid Substitution</term><term>Humans</term><term>Molecular Sequence Data</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Données de séquences moléculaires</term><term>Humains</term><term>Liaison aux protéines</term><term>Protéines proto-oncogènes c-raf</term><term>Relation structure-activité</term><term>Sites de fixation</term><term>Substitution d'acide aminé</term><term>Séquence d'acides aminés</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Seven amino acid peptides were tested as in vitro inhibitors of oncogenic Ras-Raf association. The sequences of these peptides were derived from the H-Ras effector region (amino acids 25 to 51) and the Ras binding domain of Raf-1 (amino acids 64 to 105). Eleven out of the twenty-one Ras 7-mers tested inhibited formation of the Ras-Raf complex by at least 20% at 100 microM. The most potent of these inhibitory peptides contained the effector residues 32 to 37 or 40 to 45. Of the Raf-1 peptides tested, only the 94-ECCAVFR-100 and 95-CCAVFRL-101 peptides were significant inhibitors of Ras-Raf binding. The 95-101 Raf peptide had an IC50 value of 7 microM and also inhibited Ras-RalGDS binding. Analysis of the 95-101 peptide showed that its inhibitory activity required at least one cysteine followed by several hydrophobic residues. Our results demonstrate the feasibility of using small molecules as inhibitors of Ras protein-protein interactions.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Baker, L" sort="Baker, L" uniqKey="Baker L" first="L" last="Baker">L. Baker</name><name sortKey="Marshall, M S" sort="Marshall, M S" uniqKey="Marshall M" first="M S" last="Marshall">M S Marshall</name><name sortKey="Sun, H" sort="Sun, H" uniqKey="Sun H" first="H" last="Sun">H. Sun</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Barnard, D" sort="Barnard, D" uniqKey="Barnard D" first="D" last="Barnard">D. Barnard</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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