Antidiuretic and pressor activities of vasopressin analogs with L‐alaninamide and D‐alaninamide substitutions at position 9

Buku, Angeliki; Gazis, Diana; Schwartz, Irving L.

doi:10.1111/j.1399-3011.1984.tb02757.x

Cited by 15 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Boc . Syntheses were performed on a Vega 96 automatic peptide synthesizer using BHA resin from polystyrene-1 % divinylbenzene (1 3) purchased from Beckman, according to a well established procedure which has been used for the synthesis of many AVP analogs (14). An individual cycle for each amino acid included deprotection of the Boc group with 50% trifluoroacetic acid in CH,Cl,, and acylation with 5-fold excess of the protected amino acids.…”

Section: Amino Acids Protecting Groups and Reagents The N U -mentioning

confidence: 99%

See 1 more Smart Citation

Probes for vasopressin receptors Attachment of affinity and fluorescent groups in vasopressin

Buku

Gazis

1990

International Journal of Peptide and Protein Research

Self Cite

View full text Add to dashboard Cite

Fluorescent, photoreactive, and biotinylated analogs of vasopressin have been prepared in which one of these three groups has been attached to a reactive amino group in either position 4 or position 7. Using solid phase methodology, we have synthesized two active parent compounds, [l‐desamino,4‐lysine,7‐hydroxy‐prolinelarginine vasopressin and [l‐desamino,7‐aminoproline]arginine vasopressin, and acylated them to obtain biotinyl, azidobenzoyl, and fluoresceinyl derivatives. We have also prepared analogs in which a “spacer arm” was inserted between lysine in position 4 and the marker group. Some of these derivatives have good antidiuretic activity and could be valuable probes in studying hormone‐receptor interaction and in receptor visualization and purification.

show abstract

Section: Amino Acids Protecting Groups and Reagents The N U -mentioning

confidence: 99%

“…The peptide was then cleaved from the resin and treated in the same way as the other analogs. Peptides were purified by partition chromatography and gel filtration as previously described (14). Overall yields were 35-40% based on the initial 0.67 mequiv.…”

Section: Amino Acids Protecting Groups and Reagents The N U -mentioning

confidence: 99%

Probes for vasopressin receptors Attachment of affinity and fluorescent groups in vasopressin

Buku

Gazis

1990

International Journal of Peptide and Protein Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another vasopressin based analogue discovered in the late 1950s from pigs is lypressin, (8-lysine)-vasopressin. Lypressin was found to have a lower potency than AVP and desmopressin, with lypressin having about 10% activity compared to AVP[318].…”

mentioning

confidence: 97%

Development of METx: A Vasopressin Agonist

Patel¹

2016

Preprint

View full text Add to dashboard Cite

Vasopressin (AVP) was one of the first peptides to be extracted and produced synthetically in the early 1950s. Since then AVP and its analogues have been increasingly researched as both AVP agonists and antagonists have therapeutic uses. Although much time and effort has been used to design potent selective AVP agonists and antagonists, very few have reached the market. AVP agonist analogues have only been approved for diabetes insipidus and variceal bleeding. Current main stay treatment for diabetes insipidus is desmopressin, a synthetic analogue of AVP. Desmopressin is well tolerated by the majority of patients, however severe adverse affects, such as hyponatraemia and water intoxication require a strict fluid intake, restricting fluid intake. Our aim is to develop METx for the treatment of diabetes insipidus to help overcome some of the limitations in lifestyle. The solubility and aggregation of METx was measured using the shake flask and pyrene assay respectively. The activity of METx was determined by measuring cAMP production by MDCK cells. The activity of METx was compared to that AVP, the natural agonist of the vasopressin receptor. Formulation studies were performed using GCPQ to create a formulation that could be used subcutaneously or orally. The stability of GCPQ formulations was determined in plasma, simulated gastric fluid (SGF) and rat intestinal wash (RIW). The activity of METx was measured in vivo by monitoring the urine production of rats upon administration of METx intravenously. METx was practically insoluble in aqueous solvents such as water and PBS, with increased solubility in organic solvents. Using TEM imaging aggregation of METx of was seen, the pyrene assay determined the critical micelle concentration to be 27.4mg l-1. METx was found to be a partial agonist of the vasopressin 2 receptor naturally expressed on the MDCK cells, it exhibited a similar EC 50 to AVP. Formulating with GCPQ a ratio of 1:5 (METx:GCPQ) was found to be the most stable in plasma, SGF and RIW. In vivo studies found METx to have a dose dependent reduction in urine production in rats, with 40mg kg-1 rats not producing any urine. The experiments suggest the development of a novel partial agonist of the vasopressin 2 receptor in vitro. The addition of GCPQ results in the formation of nanoparticles, with a ratio of 1:5 (METx:GCPQ) most stable in plasma, SGF and RIW. In vivo experiments resulted in reduced urine production by rats, in a dose responsive manner.

show abstract

Peptide and Protein Hormones

König

2000

Ullmann's Encyclopedia of Industrial Chemistry

View full text Add to dashboard Cite

Antidiuretic and pressor activities of vasopressin analogs with L‐alaninamide and D‐alaninamide substitutions at position 9

Cited by 15 publications

References 27 publications

Probes for vasopressin receptors Attachment of affinity and fluorescent groups in vasopressin

Probes for vasopressin receptors Attachment of affinity and fluorescent groups in vasopressin

Development of METx: A Vasopressin Agonist

Peptide and Protein Hormones

Contact Info

Product

Resources

About