New Urotensin II Peptides Available: UrantideTM, UT Agonist, and Urotensin II-Related Peptide available from Peptides International

Urotensin II Peptides Available: Urantide^TMand UT Agonist
Urotensin II-Related Peptide
New UT Antagonist
Now available from Peptides International

Vasoactive Peptides Feature

Many vasoactive peptides possess induce vasodilation by acting via specific G-protein coupled receptors (GPCR). Drug development targets these receptors, as well as the enzymes that generate vasoactive peptides, as a means to gain control over this process as a potential treatment route of hypertension. Since its discovery by Yanagisawa in 1988, endothelin-1 (ET-1) has been consistentlydescribed as the most potent vasoconstrictor yet discovered. Specific antagonists to Endothelin A and B receptors are well-known and include popular BQ-123, BQ-610, and BQ-788. At the present time, urotensin (U II) is being considered the new endothelin by many due to its ultrapotent vasoconstrictive properties. Recently, Patacchini et al. introduced Urantide^TM as a potent U II antagonist, the first reported of its kind. The importance of ET-1 and urotensin as cardiovascular andrenal peptides in humans is well established, making these peptides and their antagonists highly important research tools.

Urantide^TMand UT Agonist
Urotensin II Product Brochure (PDF)

Urotensin II (UT) has been described as one of the most potent vasoconstrictor substances known to date. The specific human urotensin II receptor was identified in 1999 by Ames et al., which was formerly identified as GPR14/SENR orphan receptor (1).

In 2002, Grieco and coworkers produced an UT receptor superagonist, H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH, incorporating penicillamine, a b-b dimethylcysteine replacement, in the minimally active UT fragment. This analogue was reported to be the most potent UT agonist known to date (2). Recently Patacchini and coworkers reported a new potent urotensin II receptor antagonist peptide, (urantide^TM) (3). Urantide was able to block hUT-II induced contractions in the rat isolated thoracic aorta and was reported to competitively antagonize hU-II induced effects (pK_B = 8.3 ±0.09 (n=12)). Both peptides are now available from Peptides International.

Urantide did not exhibit agonist activity up to 1 micromolar concentration and it is noteworthy that it possesses high affinity at human UT receptors. The exact nature of urantide's agonist/antagonist role with regards to human UT receptors has not been thoroughly investigated. Interestingly it was reported to displace [¹²⁵I]UT from specific binding at hU-II recombinant receptors transfected into CHO/K1 cells (pki=8.3±0.04) (3).

U-II immunoreactivity is also found within central nervous system and endocrine tissues implicating additional functions. It has been suggested that urotensin II is involved in human diseases such as atherosclerosis, cardiac hypertrophy, pulmonary hypertension and tumor growth (4). Therefore, urotensin II antagonists could be useful in the treatment of such diseases and both peptides should aid in clarifying UT's importance and functions in such diseases.

1. R.S. Ames, H.M. Sarau, J.K. Chambers, R.N. Willette, N.V. Aiyar, A.M. Romanic, C.S. Louden, J.J. Foley, C.F. Sauermelch, R.W. Coatney, Z. Ao, J. Disa, S.D. Holmes, J.M. Stadel, J.D. Martin, W.S. Liu, G.I. Glover, S. Wilson, D.E. Mcnulty, C.E. Ellis, N.A. Elshourbagy, U. Shabon, J.J. Trill, D.W. Hay, E.H. Ohlstein, D.J. Bergsma, and S.A. Douglas, Nature, 401, 282 (1999).
2. P. Grieco, A. Carotenuto, P. Campiglia, E. Zampelli, R. Patacchini, C.A. Maggi, E. Novellino, and P. Rovero, J. Med. Chem., 45, 4391 (2002).
3. R. Patacchini, P. Santicioli, S. Giuliani, P. Grieco, E. Novellino, P. Rovero, and C.A. Maggi, Br. J. Pharmacol., 140, 1155 (2003).
4. J.J. Maguire and A.P. Davenport, Br. J. Pharmacol., 137, 579 (2003).

Urotensin II-Related Peptide from the Peptide Institute
Urotensin II Product Brochure (PDF)

Urotensin II (UII) is the most potent vasoconstrictor known to date. The scientists at Takeda Chemical Industries in Japan recently reported the identification of the endogenous ligand for urotensin II. Using goby UII antibody, immunoreactivity experiments led to the detection of this new peptide in rat brains (1). Its primary structure resembled urotensin II (UII), therefore, the new isolated ligand was named urotensin II-related peptide (URP). The cDNA sequence of rat was determined to possess a potential dibasic flanking cleavage site at the amino terminus. Subsequent studies showed that human and mouse URPs are in fact identical to rat URP.

This newly identified peptide exhibits the following activity:
• High affinity, saturable binding activity to human and rat UII receptors (UIIR), K_d = 170 pM and 91 pM, respectively
• Ca²⁺ mobilization activity reported in CHO cells expressing human or rat UIIR with ED₅₀ = 4.8 nM (human UIIR) and 0.55 nM (rat UIIR)
• long-lasting, hypotensive effect in anaesthetized rat at 10 nmol/kg dosage levels

While tissue distribution of preproURP is abundant in both human and rat, not only is the distribution different in both and but it also is distinct from that of urotensin II. This new discovery should aid structure elucidation studies of urotensin peptides and help lead to new approaches in hypertension research.

1. T. Sugo, Y. Murakami, Y. Shimomura, M. Harada, M. Abe, Y. Ishibashi, C. Kitada, N. Miyajima, N. Suzuki, M. Mori, and M. Fujino, Biochem., Biophys. Res. Commun., 310, 860 (2003). (Original)

NEW

NEW UROTENSIN PRODUCTS AVAILABLE FROM PEPTIDES INTERNATIONAL Urotensin II Product Brochure (PDF)
CODE	PRODUCT DESCRIPTION	QTY	USD
Urotensins - Potent Vasoconstrictors
PUT-3928-PI New!	H-Tic-[Pen-Phe-D-Trp-Orn-Tyr-Cys]-Val-OH Potent Urotensin II Antagonist Recent studies replacing the Asp amino acid in Urantide led to the discovery of a new urotensin II antagonist, H-Tic-[Pen-Phe-D-Trp-Orn-Tyr-Cys]-Val-OH. It was found to be more potent than Urantide at inducing contractions in isolated rat thoracic aorta, with a pA2 value of 9.0 compared to a pA2 value of 8.3 for Urantide. • This product is sold under exclusive license granted to Peptides International, Inc. Patent N. FI2007A000032. Patent N. FI2006A000340	1 mg	125
PUT-3639-PI	Urantide^TM H-Asp-[Pen-Phe-D-Trp-Orn-Tyr-Cys]-Val-OH [Pen⁵, D-Trp⁷, Orn⁸]-Urotensin II (Human, 4-11) H-Asp-[Pen-Phe-D-Trp-Orn-Tyr-Cys]-Val-OH (Disulfide bonds between Pen²-Cys⁷) (M.W. 1075.28) C₅₁H₆₆N₁₀O₁₂S₂ Potent Urotensin II Antagonist R. Patacchini, P. Santicioli, S. Giuliani, P. Grieco, E. Novellino, P. Rovero, and C.A. Maggi, Br. J. Pharmacol., 140, 1155 (2003). • This product is sold under exclusive license granted to Peptides International, Inc.	1 mg	125
PUT-3640-PI	H-Asp-[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH (Disulfide bonds between Pen²-Cys⁷) (M.W. 1089.31) C₅₂H₆₈N₁₀O₁₂S₂ *Potent Urotensin II Agonist* P. Grieco, A. Carotenuto, P. Campiglia, E. Zampelli, R. Patacchini, C.A. Maggi, E. Novellino, and P. Rovero, J. Med. Chem., 45, 4391 (2002). • This product is sold under exclusive license granted to Peptides International, Inc.	1 mg	125
PUT-4408-v	Urotensin II-Related Peptide (Human, Rat) H-Ala-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH (Disulfide bond between Cys² - Cys⁷) (M.W. 1017.2) C₄₉H₆₄N₁₀O₁₀S₂ Potent Vasoconstrictor Endogenous Ligand for U-II Rat Receptor T. Sugo, Y. Murakami, Y. Shimomura, M. Harada, M. Abe, Y. Ishibashi, C. Kitada, N. Miyajima, N. Suzuki, M. Mori, and M. Fujino, Biochem. Biophys. Res. Commun., 310, 860 (2003).	0.5 mg vial	129
PUT-4365-v	Urotensin II (Human) Potent Vasoconstrictor	0.5 mg vial	209
PUT-4371-v	Urotensin II (Rat) Potent Vasoconstrictor	0.5 mg vial	209
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Please contact Peptides International for ordering information. Peptides International, Inc. PO Box 24658 Louisville, Kentucky 40224 USA Phone: 502-266-8787 or 800-777-4779 Fax: 502-267-1FAX (1329) Email: peptides@pepnet.com
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