Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

Chini, Bice; Chinol, Marco; Cassoni, Paola; Papi, Stefano; Reversi, Alessandra; Areces, Liliana B.; Marrocco, Tiziana; Paganelli, Giovanni; Manning, Maurice; Bussolati, Gianni

doi:10.1038/sj.bjc.6601189

Cited by 31 publications

(42 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4, c, d, e, and f). Doseresponse experiments indicated that DNalOVT had an EC 50 for G␣ i1 activation of 38.83 Ϯ 16.0 nM (n ϭ 3) (Fig. 5a), very similar to the 62.63 Ϯ 39.00 nM obtained using OT (Fig.…”

Section: Table 1 Ot-and Atosiban-derived Peptidessupporting

confidence: 63%

“…36). The finding of the same EC 50 by means of BRET activation and IP measurements strongly validates the use of the G q biosensor in determining OTR ligand efficacy.…”

Section: Discussionmentioning

confidence: 54%

“…The EC 50 values of activation of the different G i /G o isoforms ranged from 11.5 nM (for G␣ i3 ) to 91.8 nM (for G␣ oB ); the local concentration of the peptide, the level of expression of the individual isoforms, and their localization in specific plasma membrane domains with or without the receptor will thus all be important for determining the subunit-specific G i /G o coupling of endogenous OTR. Similarly, the at least 10-fold higher EC 50 values of all of the G␣ i and G␣ o isoforms in comparison with G␣ q indicates that G i /G o -mediated pathways are activated at higher OT concentrations than the G q pathway.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, these data confirm the functional selective properties of atosiban and identify its selectivity for the OTR-G i3 complex. In this regard, it is important to note that the EC 50 /K i ratio of atosiban for the OTR-G i3 complex, 53, is in the same order of magnitude as that of OT, 14, which indicates a similar right shift in the EC 50 value with respect to the apparent affinity of the two analogues.…”

Section: Table 1 Ot-and Atosiban-derived Peptidesmentioning

confidence: 99%

“…Fig. 6, c and d, shows the dose-response curves of OT-induced ␤-arrestin1 and ␤-arrestin2 recruitment, whose calculated EC 50 . of three independent experiments, each performed in sextuplicate.…”

Section: Table 1 Ot-and Atosiban-derived Peptidesmentioning

confidence: 99%

See 4 more Smart Citations

Functional Selective Oxytocin-derived Agonists Discriminate between Individual G Protein Family Subtypes

Busnelli

Saulière

Manning

et al. 2012

Journal of Biological Chemistry

158

142

View full text Add to dashboard Cite

Background:The oxytocin receptor couples to multiple G proteins, leading to different physiological responses. Results: We screened for functional selective oxytocin receptor agonists and identified two analogs that activate individual G i subunits. Conclusion: Functional selective analogs discriminate among different receptor conformations coupled to G i proteins. Significance: These compounds will contribute to the development of selective drugs with new selectivity and therapeutic profiles.

show abstract

Section: Table 1 Ot-and Atosiban-derived Peptidessupporting

confidence: 63%

“…36). The finding of the same EC 50 by means of BRET activation and IP measurements strongly validates the use of the G q biosensor in determining OTR ligand efficacy.…”

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Table 1 Ot-and Atosiban-derived Peptidesmentioning

confidence: 99%

Section: Table 1 Ot-and Atosiban-derived Peptidesmentioning

confidence: 99%

See 3 more Smart Citations

Functional Selective Oxytocin-derived Agonists Discriminate between Individual G Protein Family Subtypes

Busnelli

Saulière

Manning

et al. 2012

Journal of Biological Chemistry

158

142

View full text Add to dashboard Cite

show abstract

Impact of the Merrifield solid phase method on the design and synthesis of selective agonists and antagonists of oxytocin and vasopressin: A historical perspective

Manning

2008

Biopolymers

View full text Add to dashboard Cite

This tribute to Bruce Merrifield traces the author's fortuitous path in 1964 from Vincent du Vigneaud's laboratory to the laboratory of D. W. Woolley to learn the solid phase method and then to his first faculty position in the Department of Biochemistry, McGill University, Montreal in 1965. It recalls the key roles played from early 1966 to July 1967 by Bruce Merrifield, John Stewart, Arnold Marglin, Herb Takashima, and Vincent du Vigneaud in providing key advice to the author's efforts to use the solid phase method to synthesize oxytocin; while simultaneously the du Vigneaud and Merrifield laboratories were collaborating on the solid phase synthesis of deamino‐oxytocin. Both syntheses were published in the same issue of the Journal of American Chemical Society in 1968. Also described is how this breakthrough impacted the author's scientific career: by leading to highly productive collaborative studies, initially with Wilbur H. Sawyer and subsequently with others, on the design and synthesis of selective agonists, antagonists, and radioiodinated ligands for oxytocin and vasopressin receptors. These syntheses were greatly facilitated by the contributions of highly talented graduate students, research technicians, and visiting peptide chemists from Hungary, England, Poland, Bulgaria, and China. Many of these peptides have become very valuable pharmacological tools in studies on the peripheral and central effects of oxytocin and vasopressin: further attesting to the profound impact of the solid phase method as the cornerstone for all the discoveries, which he and his collaborators and coworkers have made over the past 40 years. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 203–212, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

show abstract

Design of peptide oxytocin antagonists with strikingly higher affinities and selectivities for the human oxytocin receptor than atosiban

et al. 2005

View full text Add to dashboard Cite

The peptide oxytocin (OT) antagonist atosiban, approved for tocolytic use in Europe (under the tradename Tractocile), represents an important new therapeutic advance for the treatment of premature labor. This paper presents some new peptide OT antagonists which offer promise as superior tocolytics. The solid phase synthesis is reported of four pairs of L and D-2-naphthylalanine (L/D-2Nal) position-2 modified analogs of the following four oxytocin (OT) antagonists: des-9-glycinamide [1-(beta-mercapto-beta,beta-pentamethylene propionic acid), 2-O-methyltyrosine, 4-threonine]ornithine-vasotocin (desGly-NH(2),d(CH(2))(5)[Tyr(Me)(2),Thr(4)]OVT) (A); the Tyr-NH(2) (9) analog of (A), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2) (9)]OVT (B); the Eda(9) analog of (A), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Eda(9)]OVT (C); and the retro COCH(2)Ph(4-0H)(10) modified analog of (C), d(CH(2))(5)[Tyr(Me)(2),Thr(4),Eda(9)<-- COCH(2)Ph(4-0H)(10)]OVT (D). The eight new analogs of A-D are (1) desGly-NH(2),d(CH(2))(5)[D-2Nal(2),Thr(4)]OVT, (2) desGly-NH(2),d(CH(2))(5)[2-Nal(2),Thr(4)]OVT, (3) d(CH(2))(5)[D-2Nal(2),Thr(4),Tyr-NH(2) (9)]OVT, (4) d(CH(2))(5)[2Nal(2),Thr(4),Tyr-NH(2) (9)]OVT, (5) d(CH(2))(5)[D-2Nal(2),Thr(4),Eda(9)]OVT, (6) d(CH(2))(5)[2Nal(2),Thr(4),Eda(9)]OVT, (7) d(CH(2))(5)[D-2Nal(2),Thr(4),Eda(9)<-- COCH(2)Ph(4-0H)(10)]OVT, (8) d(CH(2))(5)[2Nal(2),Thr(4),Eda(9)<-- COCH(2)Ph(4-OH)(10)]OVT. Peptides 1-8 were evaluated for agonistic and antagonistic activities in in vitro and in vivo rat bioassays, in rat OT receptor (rOTR) binding assays and in human OT receptor (hOTR) and human vasopressin (VP) vasopressor (V(1a)) receptor (hV(1a)R) binding assays. Also reported are the hOTR and hV(1a)R affinity data for atosiban and for B. None of the eight peptides exhibit oxytocic or vasopressor agonism. Peptides 1-8 exhibit weak antidiuretic agonism (activities in the range 0.014-0.21 U/mg). Peptides 1-6 exhibit potent in vitro (no Mg(2+)) OT antagonism (anti-OT pA(2) values range from 7.63 to 8.08). Peptides 7 and 8 are weaker OT antagonists. Peptides 1-6 are all OT antagonists in vivo (estimated in vivo anti-OT pA(2) values in the range 6.94-7.23). Peptides 1-8 exhibit vasopressor antagonism, anti-V(1a) pA(2) values in the range 5.1-7.65. Peptides 1-8 exhibit high affinities for the rOTR (K(i) values = 0.3-7.8 nM). Peptides 1-4 and B exhibit surprisingly very high affinities for the hOTR; their K(i) values are 0.17, 0.29, 0.07, 0.14 and 0.59 nM, respectively. Peptides 1-4 and B exhibit respectively 449, 263, 1091, 546 and 129 times greater affinity for the hOTR than atosiban (K(i) = 76.4 nM). Peptides 1-4 exhibit high affinities for the hV(1a)R (K(i)s = 1.1 nM, 1.3 nM, 0.19 nM and 0.54 nM, all higher than the hV1(a)R affinities exhibited by atosiban (K(i) = 5.1 nM) and by B (K(i) = 5.26 nM). Because of their strikingly higher affinities for the hOTR than atosiban, peptides 1-4 and B exhibit gains in anti hOT/anti hV(1a) receptor selectivity compared with atosiban of 93, 64, 39, 56 and 127, respectively. These OT antagonists are thus promisi...

show abstract

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue

Cited by 31 publications

References 20 publications

Functional Selective Oxytocin-derived Agonists Discriminate between Individual G Protein Family Subtypes

Functional Selective Oxytocin-derived Agonists Discriminate between Individual G Protein Family Subtypes

Impact of the Merrifield solid phase method on the design and synthesis of selective agonists and antagonists of oxytocin and vasopressin: A historical perspective

Design of peptide oxytocin antagonists with strikingly higher affinities and selectivities for the human oxytocin receptor than atosiban

Contact Info

Product

Resources

About