Synthesis and Biological Properties of 1-Desamino-8-lysine-vasopressin

Kimbrough, Raymond D.; Cash, William D.; Branda, Luis A.; Çhan, W. Y.; Vigneaud, Vincent du

doi:10.1016/s0021-9258(18)81197-8

Cited by 62 publications

(13 citation statements)

References 23 publications

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“…75,76 We have no explanation for these striking differences in antidiuretic activities. The vasopressor activities of the resynthesized position 8 analogues of dAVP are in general much closer to the values in the original publications [73][74][75][76] (Table 1).…”

Section: Resultssupporting

confidence: 79%

“…The rat V 1b , V 2 , V 1a , and OT receptor affinities for the position 8 modified peptides 1-13, together with those of their parent peptides d and d[Arg 4 ]AVP (D) 67,68 and the related peptides, AVP, 57,87 dAVP, 72,86 dDAVP, 86,95a 76 Thus, for the Lys 8 and Orn 8 analogues, our values are higher than those originally reported. 73,74 For the Dab 8 and Dap 8 analogues, the values are strikingly lower than the original values. 75,76 We have no explanation for these striking differences in antidiuretic activities.…”

Section: Resultsmentioning

confidence: 84%

“…These two peptides and indeed peptide D are clearly far more potent antidiuretic agonists than AVP (antidiuretic activity ) 332 units/ mg). 86 These findings on the contrasting effects on antidiuretic activities of the Lys 8 , Orn 8 , Dab 8 , and Dap 8 substitutions in dAVP [73][74][75][76] 4 ]AVP (B), closely mirror the effects on vasopressor activities of these four substituents at position 8 in dAVP [73][74][75][76] (Table 1). Thus, there is no correlation between the number of carbons in the side chain at position 8 and the vasopressor potency of the resultant analogue.…”

Section: Effects Of Position 8 Modifications Of Peptides A-d On Antid...mentioning

confidence: 84%

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Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

et al. 2007

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The neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin (OT) mediate a wide variety of peripheral and central physiological and behavioral effects by acting on four different G-protein coupled receptors, termed V1a (vascular), V1b (pituitary), V2 (renal), and OT (uterine). We recently reported that d[Cha4]AVP (A), d[Leu4]AVP (B), d[Orn4]AVP (C), and d[Arg4]AVP (D) have high affinity and are selective agonists for the human V1b receptor. However, peptides A-D were subsequently shown to be potent antidiuretic agonists in the rat and are, thus, not selective V1b agonists in the rat. Peptides A-D served as leads for the studies reported here. They were modified at position 8 by Lys, ornithine (Orn), diaminobutyric acid (Dab), and diaminopropionic acid (Dap) to give d[Cha4,Lys8]VP (1), d[Cha4,Orn8]VP (2), d[Cha4,Dab8]VP (3), d[Cha4,Dap8]VP (4), d[Leu4,Lys8]VP (5), d[Leu4,Orn8]VP (6), d[Leu4,Dab8]VP (7), d[Leu4,Dap8]VP (8), d[Orn4,Lys8]VP (9), d[Orn4,Orn8]VP (10), d[Arg4,Lys8]VP (11), d[Arg4,Orn8]VP (12), and d[Arg4,Dab8]VP (13). All peptides were synthesized by the Merrifield solid-phase method. Their binding and functional properties were evaluated in rat AVP V1a, V1b, and V2 receptors and on the rat OT receptor expressed either in native tissues or in stably transfected cells. They were also examined in rat vasopressor, antidiuretic, and in in vitro (no Mg++) oxytocic assays. Functional studies performed on chinese hamster ovary cells expressing the different AVP/OT receptors confirm that d[Cha4,Lys8]VP (1), d[Cha4,Dab8]VP (3), d[Leu4,Lys8]VP (5), and d[Leu4,Dap8]VP (8) are the first selective agonists for the rat V1b receptor. These selective V1b agonists are promising new tools for studies of the role of the V1b receptor in the rat.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 84%

Section: Effects Of Position 8 Modifications Of Peptides A-d On Antid...mentioning

confidence: 84%

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Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

et al. 2007

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“…One of the findings from these studies was that the free a-amino group of the neurohypophysial hormones is not essential for the manifestation of the biological effects associated with these hormones (Hope et al, 1962;Kimbrough et al, 1963). It was further shown that replacement of the a-amino group by hydrogen in the structure of these hormones results in considerably higher biological activities than the natural compounds (Hope et al, 1962;Kimbrough et al, 1963).…”

mentioning

confidence: 99%

Synthesis of deamino-A¹ sheep insulin

Katsoyannis¹,

Zalut²

1972

Biochemistry

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“…In order that the easily removable Boc group could also be employed on the e-amino nitrogen of the lysine residue, a synthetic scheme similar to the one developed by Jones et al 19 for a synthesis of A VP "Activities are in units/mg ± SE. "Kimbrough et al 34 "Higher values ranging up to 308 units/mg35 have also been reported, and most fall within the range of 250-290 units/mg originally reported by Bartlett et al 36 Uncontrolled differences in H20 and HO Ac content of the lyophilized samples used for assay may account for some of the variability. "Huguenin and Boissonnas.8 was used.…”

mentioning

confidence: 68%

Synthesis and some pharmacological properties of [3-.beta.-(2-thienyl)-L-alanine]-8-lysine-vasopressin

Smith¹,

Ferger²,

Çhan³

1975

J. Med. Chem.

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[3-beta-(2-Thienyl)-L-alanine]-8-lysine-vasopressin was synthesized by solution techniques. The partially protected heptapeptide Boc-Cys(Ec)-Tyr-Thi-Gln-Asn-Cys(Ec)-Pro (1) was synthesized in a stepwise manner using the active ester method or the dicyclohexylcarbodiimide (DCC) coupling technique mediated by 1-hydroxybenzotriazole (HBt). The protected nonapeptide amide Boc-Cys(Ec)-Tyr-Thi-Gin-Asn-Cys(Ec)-Pro-Lys(Coc)-Gly-NH2 (2) was prepared by coupling 1 with Lys(Coc)-Gly-NH2 using DCC-HBt. From 2, [3-thienylalanine]-8-lysine-vasopressin was obtained by removing the Boc-protecting groups with trifluoroacetic acid and ethylcarbamoyl (Ec) protecting groups in refluxing liquid NH3 followed by oxidative cyclization in H2O-MeOH using ICH2CH2I. Purification was effected by partition chromatography followed by gel filtration. The highly purified product possesses activities in the oxytocic, avian vasodepressor, rat pressor, and antidiuretic assays of 19.0 +/- 0.5, 87 +/- 4, 243 +/- 5, and 332 +/- 32 units/mg, respectively. Thus [3-thienylalanine]-8-lysine-vasopressin has higher oxytocic, avian vasodepressor, and antidiuretic potencies than does 8-lysine-vasopressin, whereas its pressor potency is about the same as or slightly lower than that of 8-lysine-vasopressin.

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Synthesis and Biological Properties of 1-Desamino-8-lysine-vasopressin

Cited by 62 publications

References 23 publications

Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Synthesis of deamino-A¹ sheep insulin

Synthesis and some pharmacological properties of [3-.beta.-(2-thienyl)-L-alanine]-8-lysine-vasopressin

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Synthesis and Biological Properties of 1-Desamino-8-lysine-vasopressin

Cited by 62 publications

References 23 publications

Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Synthesis of deamino-A1 sheep insulin

Synthesis and some pharmacological properties of [3-.beta.-(2-thienyl)-L-alanine]-8-lysine-vasopressin

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Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V_1bReceptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8

Synthesis of deamino-A¹ sheep insulin