Structure-activity relationships for the competitive angiotensin antagonist [sarcosine1, O-methyltyrosine4]angiotensin II (sarmesin)

Goghari, Mahesh H.; Franklin, K. J.; Moore, Graham J.

doi:10.1021/jm00156a035

Cited by 24 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Analyses of the effects of different ANG II analogs bearing single or multiple modifications indicated that an electrostatic interaction between the ANG II COOH-terminal carboxylate group and the receptor is an important factor for high-affinity binding (100) and that the peptide's Arg 2 , Tyr 4 , and His 6 side chains are also important for high-affinity binding (31,178,239,240). On the other hand, replacements of Tyr 4 and mainly Phe 8 by aliphatic residues were shown to generate competitive antagonists, thus attesting to the importance of these aromatic residues for receptor activation (70,247). The Val 3 , Ile 5 , and Pro 7 residues were found to be neither crucial for binding nor for activation.…”

Section: A Receptor Binding and Activationmentioning

confidence: 99%

“…Later on, sarmesin, a potent antagonist with hydroxymethylated Tyr 4 ([Sar 1 ,Tyr(Me) 4 ]-ANG II), was described (252). Combined modifications on both Tyr 4 and Phe 8 were shown to be nonadditive, generating antagonists of lower potencies (70,247).…”

Section: B Antagonism By Ang II Analogsmentioning

confidence: 99%

“…In AT 1 receptor activation, a role of aromatic side chains at the receptor and at the agonist in pushing the structure towards an expanded form is observed. For instance, ANG II's Phe 8 and Tyr 4 (and His 6 ) aromatic side chains are involved in receptor activation (70,178,247) through interactions with helix V's Phe 204A(517) , helix VI's Phe 249A(614) , Trp 253A(618) , His 256A(621) and Phe 259A(624) , and helix VII's Tyr 292A(723) side chains (82,175,178,195,196) (Fig. 7B).…”

Section: Physiological Activation Of Agpcrs and At 1 Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

Oliveira¹,

Costa-Neto²,

Nakaie³

et al. 2007

Physiological Reviews

View full text Add to dashboard Cite

The most prevalent physiological effects of ANG II, the main product of the renin-angiotensin system, are mediated by the AT1 receptor, a rhodopsin-like AGPCR. Numerous studies of the cardiovascular effects of synthetic peptide analogs allowed a detailed mapping of ANG II's structural requirements for receptor binding and activation, which were complemented by site-directed mutagenesis studies on the AT1 receptor to investigate the role of its structure in ligand binding, signal transduction, phosphorylation, binding to arrestins, internalization, desensitization, tachyphylaxis, and other properties. The knowledge of the high-resolution structure of rhodopsin allowed homology modeling of the AT1 receptor. The models thus built and mutagenesis data indicate that physiological (agonist binding) or constitutive (mutated receptor) activation may involve different degrees of expansion of the receptor's central cavity. Residues in ANG II structure seem to control these conformational changes and to dictate the type of cytosolic event elicited during the activation. 1) Agonist aromatic residues (Phe8 and Tyr4) favor the coupling to G protein, and 2) absence of these residues can favor a mechanism leading directly to receptor internalization via phosphorylation by specific kinases of the receptor's COOH-terminal Ser and Thr residues, arrestin binding, and clathrin-dependent coated-pit vesicles. On the other hand, the NH2-terminal residues of the agonists ANG II and [Sar1]-ANG II were found to bind by two distinct modes to the AT1 receptor extracellular site flanked by the COOH-terminal segments of the EC-3 loop and the NH2-terminal domain. Since the [Sar1]-ligand is the most potent molecule to trigger tachyphylaxis in AT1 receptors, it was suggested that its corresponding binding mode might be associated with this special condition of receptors.

show abstract

Section: A Receptor Binding and Activationmentioning

confidence: 99%

Section: B Antagonism By Ang II Analogsmentioning

confidence: 99%

Section: Physiological Activation Of Agpcrs and At 1 Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

Oliveira¹,

Costa-Neto²,

Nakaie³

et al. 2007

Physiological Reviews

View full text Add to dashboard Cite

show abstract

“…a competitive inhibitor of angiotensin II binding would be either competitive or non-competitive with ATP in a random mechanism, but would be uncompetitive with ATP in the ordered reaction. We have tried sarmesin (a non-phosphorylatable angiotensin II analogue; Goghari et al, 1986) and tyrphostin (a synthetic compound reported to be a competitive inhibitor of protein substrate binding to the EGF receptor; Gazit et al, 1989), but both were found to be non-competitive with angiotensin II in the presence of protamine (results not shown).…”

Section: Substratementioning

confidence: 99%

Alteration of the kinetic properties of the epidermal growth factor receptor tyrosine kinase by basic proteins

Hubler

Leventhal

Bertics

1992

Biochemical Journal

View full text Add to dashboard Cite

Previous studies have shown that lysine- and arginine-rich proteins can enhance the activity of tyrosine and serine/threonine protein kinases. However, the kinetics and mechanism of this activation are not fully understood. Therefore we investigated the ability of poly(amino acids) and the arginine-rich protein, protamine, to alter the kinetic properties of epidermal growth factor (EGF) receptor protein-tyrosine kinase activity using immunoaffinity-purified receptor isolated from human epidermoid carcinoma (A431) cells. Poly(L-lysine), poly(L-arginine) and protamine stimulated EGF receptor kinase activity by 3-5-fold at non-saturating doses of ATP and peptide substrate, while poly(L-glutamate) had no effect. Initial kinetic studies demonstrated an increase in the maximum velocity and a decrease in the apparent Km for the peptide substrate angiotensin II in the presence of the basic effectors. Further analysis of the kinetic mechanism by product inhibition revealed that protamine altered the pattern of ADP inhibition towards the peptide substrate but not towards ATP. The change was indicative of the receptor's ability to form an enzyme-angiotensin II-ADP ternary complex in the presence of protamine but not in its absence. In addition, the basic effectors had a substantially decreased influence on the kinase activity of a C-terminally truncated form of the EGF receptor. Thus the changes in kinase activity may be partially mediated by the C-terminal region of the receptor, which contains the sites of receptor self-phosphorylation. These results suggest that the basic domains of proteins can interact with the EGF receptor to induce changes in its kinetic properties, especially with regard to reactant recognition and binding.

show abstract

“…Επιπλέον το αμινοξύ στη θέση 1 συντελεί στη σταθεροποίηση της στερεοχημικής διαμόρφωσης του μορίου της αγγειοτενσίνης II με τις ηλεκτροστατικές αλληλεπιδράσεις, οι οποίες αναπτύσσονται μεταξύ του Ν-και C-τελικού αμινοξέος [280] . Μία άποψη για το ρόλο που διαδρα ματίζει το Ν-τελικό αμινοξύ στην πεπτιδική αλληλουχία του μορίου της Α II είναι ότι, απωθεί την πλευρική αλυσίδα της Tyr 4 προς την πλευ ρική αλυσίδα της His 6 διευκολύνοντας έτσι τις αλληλεπιδράσεις μεταξύ των δύο αυτών αρωματικών αμινοξέων [297].…”

Section: α23 το σύμπλεγμα αγγειοτενσίνης II -υποδοχέαunclassified

Συνθεση Και Φαρμακολογικη Δραση Αναλογων Της Αγγειοτενσινης Ιι Με Περιορισμενη Διαμορφωτικη Ελευθερια

Μπελτε¹

View full text Add to dashboard Cite

Μέρος των αποτελεσμάτων παρουσιάσθηκε στο 20° Ευρωπαϊκό Πεπτιδικό Συνέδριο και σε Εθνικό Συνέδριο και δημοσιεύθηκε στα περιοδικά Journal of Medicinal Chemistry και Collection of Czechoslovac Chemical Communications. Προς τον Καθηγητή μου κ. Παύλο Κορδοπάτη εκφράζω τις θερμότερες ευχαριστίες μου τόσο για την υπόδειξη του θέματος, όσο και τη συνεχή καθοδήγηση, τις πολύτιμες συμβουλές του και την πολύπλευρη επιστημο νική βοήθεια που μου παρέσχε σε όλη τη διάρκεια εκπόνησης της παρού σας διατριβής. Ο βιολογικός έλεγχος των νέων ορμονικών αναλόγων έγινε στο τμήμα Φαρμακολογίας του Πανεπιστημίου του Sherbrook (Καναδά), καθώς και στο τμήμα Ιατρικής Βιοχημείας του Πανεπιστημίου του Calgary (Καναδά). Τους Διευθυντές των ανωτέρω Τμημάτων αντίστοιχα Καθηγητές κ. E. Escher και κ. G. J. Moore, ευχαριστώ θερμά. Ιδιαίτερα ευχαριστώ το σύζυγο μου Γιάννη Τζωρτζάκη, τόσο για την αμέριστη συμπαράσταση του κατά τη διάρκεια της εκπόνησης της διατρι βής, όσο και για το σχεδιασμό των σχημάτων και την επιμέλεια της γραφής του κειμένου με τον Η/Υ. Ευχαριστίες οφείλονται επίσης στη φιλόλογο κ. Χ.Μπουχώρη για τις χρήσιμες παρατηρήσεις της και το γλωσσικό έλεγχο του κειμένου. Τέλος, ευχαριστώ όλους όσους με οιονδήποτε τρόπο συνέβαλαν στην κατά το δυνατόν άρτια παρουσίαση της παρούσας διατριβής. Πάτρα 1993 π -τολουολο • οξικό οξύ CHa-iCl}-CH 2 COOH ο ΔΡΟΜΟΣ 1 Br 2 / hv BrCH; Br CH 2 Co/f~J) Ο ΔΡΟΜΟΣ 2 CH 2 COOH BH 3 DMS BrCH 2 --Br CH 2 \~\ CH 2 COOCH 2 CO /fj} BocAACOO~X* BocAACOOCH 2^( ))-CH 2 COOCH 2 CO • CH 2 -CH 2 OH BocAACOCTX* •O 2 -\~jy CH 2 COOCH 2 CO -/Tj) Boc AA COOCH 2 -tf )> CH 2 -CH 2 OH Cr0 3 /πυριδίνη Zn/ACOH Boc AA COOCH 2 Ο CH 2 -CHO •o< Boc AA COOCH 2 -{[ ))-CH 2 -COOH 4 -( BoC • «μινοακυλοξυ -μεθυλο ) φκινυλο -οξικό οξύ NaCIO, •Ο' Boc AA COOCH 2 Ο Boc AA COOCH 2 -\{ ))-CH 2 -COOH 4-( BOC-αμινοακυλοξυ -μ£θυλο ) φαινυλο -οξικό οξύ CH 2 -COOH + Η 2 Ν -CH 2 -@ DIC V BocAACOOCH 2 -ο CH 2 -CO-NH-CHj-d) Σχήμα (Α.1.8). Παρασκευή PAM ρητινών σύμφωνα με τις μεθόδους των Tarn και συν.

show abstract

Structure-activity relationships for the competitive angiotensin antagonist [sarcosine1, O-methyltyrosine4]angiotensin II (sarmesin)

Cited by 24 publications

References 0 publications

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

Alteration of the kinetic properties of the epidermal growth factor receptor tyrosine kinase by basic proteins

Συνθεση Και Φαρμακολογικη Δραση Αναλογων Της Αγγειοτενσινης Ιι Με Περιορισμενη Διαμορφωτικη Ελευθερια

Contact Info

Product

Resources

About

Structure-activity relationships for the competitive angiotensin antagonist [sarcosine1, O-methyltyrosine4]angiotensin II (sarmesin)

Cited by 24 publications

References 0 publications

The Angiotensin II AT1Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

The Angiotensin II AT1Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

Alteration of the kinetic properties of the epidermal growth factor receptor tyrosine kinase by basic proteins

Συνθεση Και Φαρμακολογικη Δραση Αναλογων Της Αγγειοτενσινης Ιι Με Περιορισμενη Διαμορφωτικη Ελευθερια

Contact Info

Product

Resources

About

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure

The Angiotensin II AT₁Receptor Structure-Activity Correlations in the Light of Rhodopsin Structure