Biological activities of kinins and substance P octapeptides (4–11) in which phenylalanine residues have been replaced with L-carboranylalanine

1979 ◽  
Vol 57 (12) ◽  
pp. 1437-1442 ◽  
Author(s):  
R. Couture ◽  
J. -N. Drouin ◽  
O. Leukart ◽  
D. Regoli
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Substance P ◽  
Marked Reduction ◽  
Biological Activities ◽  
Chemical Modifications ◽  
Duration Of Action ◽  
Aromatic Residues ◽  
Prolonged Duration ◽  
Long Acting

The boron-containing amino acid carboranylalanine (Car) has been used for replacing the phenylalanine residues of bradykinin (BK), des-Arg9-BK and octa (4–11)-substance P (octa (4–11)-SP), in order to determine how the increased size and hydrophobicity of the aromatic residues will affect the biological activities of these peptides. Analogues of BK and of octa (4–11)-SP containing Car instead of Phe in positions 5 and 8 (BK) or 7 and 8 (octa (4–11)-SP) are practically inactive. A similar marked reduction of activity is observed with [Car8]-des-Arg9-BK, while [Car5]-des-Arg9-BK, although less potent than the natural BK fragment, shows a prolonged duration of action. Car has also been used to replace Phe5 in combination with the substitution of Phe8 by a Leu in the sequence des-Arg9-BK, in order to prolong the duration of action of antagonists for the B1 receptor of kinins. Moreover, a Lys has been added at the N-terminal of this sequence for further improving the affinity of the antagonism. The two chemical modifications have not produced the expected additive change of biological activity but a potent long-acting antagonist has been obtained with [Lys1,Car6,Leu9]-des-Arg10-BK.It is concluded that Car is unsuitable for replacing the phenyl residues of BK and octa (4–11)-SP, and also Phe8 of the fragment sequence des-Arg9-BK; Car appears, however, to be of some utility when used to replace Phe5 of the same sequence, as it prolongs the duration of action of agonists and of antagonists acting on the B1 receptor for kinins.

A comparison of the inhibitory effects of somatostatin-14, -25, and -28 on motility of the guinea pig ileum

1986 ◽  
Vol 64 (3) ◽  
pp. 303-306 ◽  
Author(s):  
Christopher H. S. McIntosh ◽  
Victoria Bakich ◽  
Yin Nam Kwok ◽  
John C. Brown
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Guinea Pig ◽  
Biological Activities ◽  
Threshold Concentration ◽  
Inhibitory Effects ◽  
Guinea Pig Ileum ◽  
Maximal Inhibition ◽  
Acid Fragment ◽  
Somatostatin 14

A number of studies have suggested that somatostatin-14 (SS-14) and somatostatin-28 (SS-28) exhibit a similar spectrum of biological activities but have different potencies. In the present study the effects of SS-14, SS-28, and somatostatin-25 on electrically induced contractions of the guinea pig ileum have been compared. All three peptides exhibited equipotent inhibitory effects. Inhibition was obtained at a threshold concentration less than 10−10 M, with maximal inhibition at 10−7 M and IC50 values of 6.0–6.5 × 10−10 M. The N-terminal 14 amino acid fragment of SS-28 had no effect either on motility, when added alone, or on the actions of SS-28, suggesting that this region of the molecule is not critical for biological activity.

scholarly journals A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids

2021 ◽  
pp. ASN.2020101537
Author(s):  
Jan Wysocki ◽  
Minghao Ye ◽  
Luise Hassler ◽  
Ashwani Kumar Gupta ◽  
Yuguo Wang ◽  
...  
Keyword(s):  
Human Kidney ◽  
Therapeutic Benefit ◽  
Biologically Active ◽  
Viral Escape ◽  
Albumin Binding ◽  
Gene Encoding ◽  
Duration Of Action ◽  
Prolonged Duration ◽  
Long Acting ◽  
Kidney Organoids

BackgroundThere is an urgent need for approaches to prevent and treat SARS-CoV-2 infection. Administration of soluble ACE2 protein acting as a decoy to bind to SARS-CoV-2 should limit viral uptake mediated by binding to membrane-bound full-length ACE2, and further therapeutic benefit should result from ensuring enzymatic ACE2 activity to affected organs in patients with COVID-19.MethodsA short variant of human soluble ACE2 protein consisting of 618 amino acids (hACE2 1–618) was generated and fused with an albumin binding domain (ABD) using an artificial gene encoding ABDCon, with improved albumin binding affinity. Human kidney organoids were used for infectivity studies of SARS-CoV-2 in a BSL-3 facility to examine the neutralizing effect of these novel ACE2 variants.ResultsWhereas plasma ACE2 activity of the naked ACE2 1–618 and ACE2 1–740 lasted about 8 hours, the ACE2 1–618-ABD resulted in substantial activity at 96 hours, and it was still biologically active 3 days after injection. Human kidney organoids express ACE2 and TMPRSS2, and when infected with SARS-CoV-2, our modified long-acting ACE2 variant neutralized infection.ConclusionsThis novel ACE2 1–618-ABD can neutralize SARS-CoV-2 infectivity in human kidney organoids, and its prolonged duration of action should ensure improved efficacy to prevent viral escape and dosing convenience.

Synthesis and biological properties of vasopressin analogues containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

1990 ◽  
Vol 55 (4) ◽  
pp. 1099-1105 ◽  
Author(s):  
Zdenko Procházka ◽  
Juris E. Ancans ◽  
Jiřina Slaninová ◽  
Alena Machová ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Activities ◽  
Biological Properties ◽  
Phase Synthesis ◽  
Aromatic Residues ◽  
Synthesis Methodology ◽  
Vasopressin Analogues

Solid phase synthesis methodology on a benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with the non-coded amino acid, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), in the position 2 ([Tic2, Lys8]VP (I)) and in the position 3 ([Tic3, Lys8]VP (II)). The analogue containing only one Tic in place of both aromatic residues was also isolated (des-Tyr2-[Tic3, Lys8]VP (III)). The biological activities of all analogues were negligible.

MODEL STUDIES IN VITRO WITH LONG-ACTING HORMONAL PREPARATIONS

1970 ◽  
Vol 64 (4) ◽  
pp. 656-669 ◽  
Author(s):  
J. van der Vies
Keyword(s):  
Biological Activity ◽  
Active Component ◽  
Biological Activities ◽  
Pharmacological Properties ◽  
Model Studies ◽  
Rate Of Absorption ◽  
Long Acting ◽  
Hydrolysis Of

ABSTRACT Since the biological activities of long-acting hormonal preparations, containing steroids or esters of steroids dissolved in arachis oil, depend very much on the rate of absorption from the intramuscular depot, an in vitro model for the latter has been developed. In this model the solution of the drug in oil is applied to a strip of filter paper and the spot eluted with a stream of hog plasma. Using this model, results were obtained which correlated with the observed rates of resorption in vivo. This demonstrates that the physical process underlying parenteral resorption depends on the distribution of the steroid between oil and plasma. As far as these esters of steroids are concerned, the steroid moiety of which is the ultimate active component, the hydrolysis of the ester by the esterase of the transporting plasma is another important factor. This has been studied in an in vitro system. The results obtained with both models proved valuable in understanding the pharmacological properties of a number of anabolic, androgenic and progestational steroids and steroid esters and also in explaining the differences in biological activity between closely related preparations.

Effect of a Long-Acting Octapeptide Analogue of Somatostatin on Growth Hormone and Pancreatic and Gastrointestinal Hormones in Man

1981 ◽  
Vol 61 (5) ◽  
pp. 653-656 ◽  
Author(s):  
A. J. Barnes ◽  
R. G. Long ◽  
T. E. Adrian ◽  
W. Vale ◽  
M. R. Brown ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Plasma Concentrations ◽  
Gastrointestinal Hormones ◽  
Gastric Inhibitory Polypeptide ◽  
Duration Of Action ◽  
Disease States ◽  
Subcutaneous Dose ◽  
Prolonged Duration ◽  
Pancreatic Endocrine Tumours ◽  
Long Acting

1. The biochemical specificity and duration of action of a single 5 mg subcutaneous dose of des-AA1,2,4,5,12,13-d-Trp8-somatostatin were evaluated in eight patients with symptomatic pancreatic endocrine tumours. 2. There was a reduction by more than 50% for at least 10 h in plasma concentrations of growth hormone, glucagon, gastrin and motilin and for 4–5 h in plasma insulin, pancreatic polypeptide, gastric inhibitory polypeptide and enteroglucagon. 3. This study shows that this octapeptide analogue of somatostatin, like somatostatin itself, lacks specificity in the hormones it suppresses. However, its prolonged duration of action against several hormones when given subcutaneously suggests that it may be of therapeutic use in a number of disease states where excessive plasma concentrations of one or more of these hormones occur.

Synthesis and properties of analogues of vasopressin with 1-aminocyclopropane-1-carboxylic acid in position 9

1988 ◽  
Vol 53 (11) ◽  
pp. 2604-2616 ◽  
Author(s):  
Zdenko Procházka ◽  
Juris E. Ancans ◽  
Jiřina Slaninová ◽  
Alena Machová ◽  
Tomislav Barth ◽  
...  
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Nmr Spectroscopy ◽  
Carboxylic Acid ◽  
Arginine Vasopressin ◽  
Solid Phase ◽  
Biological Activities ◽  
Solution Conformation ◽  
Lysine Vasopressin ◽  
C Nmr

Solid phase methodology on benzhydrylamine resin was used for the synthesis of three analogues of vasopressin with non-coded amino acid, 1-aminocyclopropane 1-carboxylic acid, in position 9. Two analogues of lysine-vasopressin ([Lys8, Acc9]vasopressin (I) and Gly3-[Lys8, Acc9]vasopressin (II)) and one analogue of arginine-vasopressin ([Arg8, Acc9]vasopressin (III)) have been synthesized. The dubious value of the biological activity of [Lys8, D-Ala9]vasopressin was reevaluated and [Lys8, L-Ala9]vasopressin was also synthesized and tested for the comparison. Differences in solution conformation of these two analogues were studied by 1H and 13C NMR spectroscopy. Biological activities of all analogues were either significantly lowered or almost completely eliminated. Analogues I-III were found to be completely inactive in analgesia and the CNS activities tested (active and passive avoidance).

Long-Acting Antipsychotic Medication, Restraint and Treatment in the Management of Acute Psychosis

1999 ◽  
Vol 33 (5) ◽  
pp. 660-666 ◽  
Author(s):  
Paul Fitzgerald
Keyword(s):  
Antipsychotic Medication ◽  
Patient Autonomy ◽  
Psychiatric Treatment ◽  
Relevant Literature ◽  
Duration Of Action ◽  
Chemical Restraint ◽  
Clinical Scenarios ◽  
Prolonged Duration ◽  
Disturbed Patient ◽  
Long Acting

Objective: Zuclopenthixol acetate (ZA) is the first parenteral antipsychotic medication introduced for clinical use in the treatment of aggression and agitation that has a relatively prolonged duration of action. The aim of this paper is to explore a number of important ethical and clinical issues that are raised by the use of this novel therapeutic formulation. Method: Relevant literature is explored and several issues are identified from which arguments for and against the use of medication of this type are raised. These issues are considered in general and with the use of a number of stylised clinical scenarios. Result: The use of long-acting antipsychotic medication is complicated by its impact upon patient autonomy, by considerations of informed consent and by the need to provide justice to all patients and staff in a psychiatric treatment setting. The use of ZA in the emergency treatment of psychotic patients may only be justified under specific clinical circumstances and its use is not appropriate as routine chemical restraint. Conclusions: Zuclopenthixol acetate is a novel and potentially useful treatment alternative in the acutely disturbed patient. Institutions in which ZA is used in emergency settings should develop protocols to guide clinicians in its appropriate use and provide monitoring.

BIOLOGICAL ACTIVITY OF SYNTHETIC HUMAN CORTICOTROPHIN WITH REVISED AMINO ACID SEQUENCE

1974 ◽  
Vol 75 (1) ◽  
pp. 24-32 ◽  
Author(s):  
Lotte Schenkel-Hulliger ◽  
René Maier ◽  
Pierre L. Barthe ◽  
Pierre A. Desaulles ◽  
Andrée Jarret ◽  
...  
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Lipolytic Activity ◽  
Biological Activities ◽  
Test Systems

ABSTRACT The corticotrophic, melanotrophic and lipolytic activity of synthetic human corticotrophin of revised structure has been evaluated and compared with that of synthetic porcine ACTH (uncorrected structure). The amino acid sequence of the two peptides differs at 3 sites in the 25 to 31 region. The two peptides exihibit identical biological activities in in vitro and in vivo test systems in the rat.

scholarly journals Self-assembly and biological activities of ionic liquid crystals derived from aromatic amino acids

2018 ◽  
Vol 20 (31) ◽  
pp. 20371-20381 ◽  
Author(s):  
Manuel M. Neidhardt ◽  
Katharina Schmitt ◽  
Angelika Baro ◽  
Carmen Schneider ◽  
Ursula Bilitewski ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ionic Liquid ◽  
Biological Activity ◽  
Liquid Crystals ◽  
Amino Acid ◽  
Self Assembly ◽  
Biological Activities ◽  
Aromatic Amino Acids ◽  
Ionic Liquid Crystals

Does the mesomorphic behaviour of l-amino acid-based ILCs correlate with biological activity?

Sign in / Sign up

Export Citation Format

Share Document